Brain metabolic derangements examined using 1H MRS and their (in)consistency among different rodent models of depression.

Major depressive disorder (MDD) is underlined by neurochemical changes in the brain. Proton magnetic resonance spectroscopy (1H MRS) is a useful tool for their examination as it provides information about the levels of metabolites. This review summarises the current knowledge of 1H MRS findings from rodent models of MDD, assesses the results from both a biological and a technical perspective, and identifies the main sources of bias. From a technical point of view, bias-introducing factors are the diversity of the measured volumes and their positioning in the brain, the data processing, and the metabolite concentration expression. The biological variables are strain, sex, and species, as well as the model itself, and in vivo vs. ex vivo exploration. This review identified some consistency in the 1H MRS findings in the models of MDD: lower levels of glutamine, glutamate + glutamine, and higher levels of myo-inositol and taurine in most of the brain regions of MDD models. This may suggest changes in regional metabolism, neuronal dysregulation, inflammation, and a compensatory effect reaction in the MDD rodent models.

Laterality in functional and metabolic state of the bulbectomised rat brain detected by ASL and 1H MRS: A pilot study.

OBJECTIVES: Pilot study validating the animal model of depression - the bilateral olfactory bulbectomy in rats - by two nuclear magnetic resonance methods, indirectly detecting the metabolic state of the brain. Furthermore, the study focussed on potential differences in brain laterality. METHODS: Arterial spin labelling assessed cerebral brain flow in prefrontal, sensorimotor, and piriform cortices, nucleus accumbens, hippocampus, thalamus, circle of Willis, and whole brain. Proton magnetic resonance spectroscopy provided information about relative metabolite concentrations in the cortex and hippocampus. RESULTS: Arterial spin labelling found no differences in cerebral perfusion in the group comparison but revealed lateralisation in the thalamus of the control group and the sensorimotor cortex of the bulbectomized rats. Lower Cho/tCr and Cho/NAA levels were found in the right hippocampus in bulbectomized rats. The differences in lateralisation were shown in the hippocampus: mI/tCr in the control group, Cho/NAA, NAA/tCr, Tau/tCr in the model group, and in the cortex: NAA/tCr, mI/tCr in the control group. CONCLUSION: Olfactory bulbectomy affects the neuronal and biochemical profile of the rat brain laterally and, as a model of depression, was validated by two nuclear magnetic resonance methods.

Model-informed unsupervised deep learning approaches to frequency and phase correction of MRS signals.

PURPOSE: A supervised deep learning (DL) approach for frequency and phase correction (FPC) of MRS data recently showed encouraging results, but obtaining transients with labels for supervised learning is challenging. This work investigates the feasibility and efficiency of unsupervised deep learning-based FPC. METHODS: Two novel deep learning-based FPC methods (deep learning-based Cr referencing and deep learning-based spectral registration), which use a priori physics domain knowledge, are presented. The proposed networks were trained, validated, and evaluated using simulated, phantom, and publicly accessible in vivo MEGA-edited MRS data. The performance of our proposed FPC methods was compared with other generally used FPC methods, in terms of precision and time efficiency. A new measure was proposed in this study to evaluate the FPC method performance. The ability of each of our methods to carry out FPC at varying SNR levels was evaluated. A Monte Carlo study was carried out to investigate the performance of our proposed methods. RESULTS: The validation using low-SNR manipulated simulated data demonstrated that the proposed methods could perform FPC comparably with other methods. The evaluation showed that the deep learning-based spectral registration over a limited frequency range method achieved the highest performance in phantom data. The applicability of the proposed method for FPC of GABA-edited in vivo MRS data was demonstrated. Our proposed networks have the potential to reduce computation time significantly. CONCLUSIONS: The proposed physics-informed deep neural networks trained in an unsupervised manner with complex data can offer efficient FPC of large MRS data in a shorter time.

Comparison of gross pathology inspection and 9.4 T magnetic resonance imaging in the evaluation of radiofrequency ablation lesions in the left ventricle of the swine heart.

Aims: Gross pathology inspection (patho) is the gold standard for the morphological evaluation of focal myocardial pathology. Examination with 9.4 T magnetic resonance imaging (MRI) is a new method for very accurate display of myocardial pathology. The aim of this study was to demonstrate that lesions can be measured on high-resolution MRI images with the same accuracy as on pathological sections and compare these two methods for the evaluation of radiofrequency (RF) ablation lesion dimensions in swine heart tissue during animal experiment. Methods: Ten pigs underwent radiofrequency ablations in the left ventricle during animal experiment. After animal euthanasia, hearts were explanted, flushed with ice-cold cardioplegic solution to relax the whole myocardium, fixed in 10% formaldehyde and scanned with a 9.4 T magnetic resonance system. Anatomical images were processed using ImageJ software. Subsequently, the hearts were sliced, slices were photographed and measured in ImageJ software. Different dimensions and volumes were compared. Results: The results of both methods were statistically compared. Depth by MRI was 8.771 ± 2.595 mm and by patho 9.008 ± 2.823 mm; p = 0.198. Width was 10.802 ± 2.724 mm by MRI and 11.125 ± 2.801 mm by patho; p = 0.049. Estuary was 2.006 ± 0.867 mm by MRI and 2.001 ± 0.872 mm by patho; p = 0.953. The depth at the maximum diameter was 4.734 ± 1.532 mm on MRI and 4.783 ± 1.648 mm from the patho; p = 0.858. The volumes of the lesions calculated using a formula were 315.973 ± 257.673 mm3 for MRI and 355.726 ± 255.860 mm3 for patho; p = 0.104. Volume directly measured from MRI with the "point-by-point" method was 671.702 ± 362.299 mm3. Conclusion: Measurements obtained from gross pathology inspection and MRI are fully comparable. The advantage of MRI is that it is a non-destructive method enabling repeated measurements in all possible anatomical projections.

AC Pulsed Field Ablation Is Feasible and Safe in Atrial and Ventricular Settings: A Proof-of-Concept Chronic Animal Study.

INTRODUCTION: Pulsed field ablation (PFA) exploits the delivery of short high-voltage shocks to induce cells death via irreversible electroporation. The therapy offers a potential paradigm shift for catheter ablation of cardiac arrhythmia. We designed an AC-burst generator and therapeutic strategy, based on the existing knowledge between efficacy and safety among different pulses. We performed a proof-of-concept chronic animal trial to test the feasibility and safety of our method and technology. METHODS: We employed 6 female swine - weight 53.75 ± 4.77 kg - in this study. With fluoroscopic and electroanatomical mapping assistance, we performed ECG-gated AC-PFA in the following settings: in the left atrium with a decapolar loop catheter with electrodes connected in bipolar fashion; across the interventricular septum applying energy between the distal electrodes of two tip catheters. After procedure and 4-week follow-up, the animals were euthanized, and the hearts were inspected for tissue changes and characterized. We perform finite element method simulation of our AC-PFA scenarios to corroborate our method and better interpret our findings. RESULTS: We applied square, 50% duty cycle, AC bursts of 100 µs duration, 100 kHz internal frequency, 900 V for 60 pulses in the atrium and 1500 V for 120 pulses in the septum. The inter-burst interval was determined by the native heart rhythm - 69 ± 9 bpm. Acute changes in the atrial and ventricular electrograms were immediately visible at the sites of AC-PFA - signals were elongated and reduced in amplitude (p < 0.0001) and tissue impedance dropped (p = 0.011). No adverse event (e.g., esophageal temperature rises or gas bubble streams) was observed - while twitching was avoided by addition of electrosurgical return electrodes. The implemented numerical simulations confirmed the non-thermal nature of our AC-PFA and provided specific information on the estimated treated area and need of pulse trains. The postmortem chest inspection showed no peripheral damage, but epicardial and endocardial discolorations at sites of ablation. T1-weighted scans revealed specific tissue changes in atria and ventricles, confirmed to be fibrotic scars via trichrome staining. We found isolated, transmural and continuous scars. A surviving cardiomyocyte core was visible in basal ventricular lesions. CONCLUSION: We proved that our method and technology of AC-PFA is feasible and safe for atrial and ventricular myocardial ablation, supporting their systematic investigation into effectiveness evaluation for the treatment of cardiac arrhythmia. Further optimization, with energy titration or longer follow-up, is required for a robust atrial and ventricular AC-PFA.