Introduction: In the context of functional magnetic resonance imaging (fMRI), carbon dioxide (CO2) is a well-known vasodilator that has been widely used to monitor and interrogate vascular physiology. Moreover, spontaneous fluctuations in end-tidal carbon dioxide (PETCO2) reflects changes in arterial CO2 and has been demonstrated as the largest physiological noise source for denoising the low-frequency range of the resting-state fMRI (rs-fMRI) signal. However, the majority of rs-fMRI studies do not involve CO2 recordings, and most often only heart rate and respiration are recorded. While the intrinsic link between these latter metrics and CO2 led to suggested possible analytical models, they have not been widely applied.
Methods: In this proof-of-concept study, we propose a deep-learning (DL) approach to reconstruct CO2 and PETCO2 data from respiration waveforms in the resting state.
Results: We demonstrate that the one-to-one mapping between respiration and CO2 recordings can be well predicted using fully convolutional networks (FCNs), achieving a Pearson correlation coefficient (r) of 0.946 ± 0.056 with the ground truth CO2. Moreover, dynamic PETCO2 can be successfully derived from the predicted CO2, achieving r of 0.512 ± 0.269 with the ground truth. Importantly, the FCN-based methods outperform previously proposed analytical methods. In addition, we provide guidelines for quality assurance of respiration recordings for the purposes of CO2 prediction.
Discussion: Our results demonstrate that dynamic CO2 can be obtained from respiration-volume using neural networks, complementing the still few reports in DL of physiological fMRI signals, and paving the way for further research in DL based bio-signal processing.
Gadolinium-based contrast agents (GBCAs) have become a crucial part of MRI acquisitions in neuro-oncology for the detection, characterization and monitoring of brain tumors. However, contrast-enhanced (CE) acquisitions not only raise safety concerns, but also lead to patient discomfort, the need of more skilled manpower and cost increase. Recently, several proposed deep learning works intend to reduce, or even eliminate, the need of GBCAs. This study reviews the published works related to the synthesis of CE images from low-dose and/or their native -non CE- counterparts. The data, type of neural network, and number of input modalities for each method are summarized as well as the evaluation methods. Based on this analysis, we discuss the main issues that these methods need to overcome in order to become suitable for their clinical usage. We also hypothesize some future trends that research on this topic may follow.
Introduction: Epilepsy is defined as non-lesional (NLE) when a lesion cannot be localized via standard neuroimaging. NLE is known to have a poor response to surgery. Stereotactic electroencephalography (sEEG) can detect functional connectivity (FC) between zones of seizure onset (OZ) and early (ESZ) and late (LSZ) spread. We examined whether resting-state fMRI (rsfMRI) can detect FC alterations in NLE to see whether noninvasive imaging techniques can localize areas of seizure propagation to potentially target for intervention.
Methods: This is a retrospective study of 8 patients with refractory NLE who underwent sEEG electrode implantation and 10 controls. The OZ, ESZ, and LSZ were identified by generating regions around sEEG contacts that recorded seizure activity. Amplitude synchronization analysis was used to detect the correlation of the OZ to the ESZ. This was also done using the OZ and ESZ of each NLE patient for each control. Patients with NLE were compared to controls individually using Wilcoxon tests and as a group using Mann-Whitney tests. Amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree of centrality (DoC), and voxel-mirrored homotopic connectivity (VMHC) were calculated as the difference between NLE and controls and compared between the OZ and ESZ and to zero. A general linear model was used with age as a covariate with Bonferroni correction for multiple comparisons.
Results: Five out of 8 patients with NLE showed decreased correlations from the OZ to the ESZ. Group analysis showed patients with NLE had lower connectivity with the ESZ. Patients with NLE showed higher fALFF and ReHo in the OZ but not the ESZ, and higher DoC in the OZ and ESZ. Our results indicate that patients with NLE show high levels of activity but dysfunctional connections in seizure-related areas.
Discussion: rsfMRI analysis showed decreased connectivity directly between seizure-related areas, while FC metric analysis revealed increases in local and global connectivity in seizure-related areas. FC analysis of rsfMRI can detect functional disruption that may expose the pathophysiology underlying NLE.
[This corrects the article DOI: 10.3389/fnimg.2022.983324.].
Introduction: Mitochondria are extremely important organelles in the regulation of bone marrow and brain activity. However, live imaging of these subcellular features with high resolution in scattering tissues like brain or bone has proven challenging.
Methods: In this study, we developed a two-photon fluorescence microscope with adaptive optics (TPFM-AO) for high-resolution imaging, which uses a home-built Shack-Hartmann wavefront sensor (SHWFS) to correct system aberrations and a sensorless approach for correcting low order tissue aberrations.
Results: Using AO increases the fluorescence intensity of the point spread function (PSF) and achieves fast imaging of subcellular organelles with 400 nm resolution through 85 μm of highly scattering tissue. We achieved ~1.55×, ~3.58×, and ~1.77× intensity increases using AO, and a reduction of the PSF width by ~0.83×, ~0.74×, and ~0.9× at the depths of 0, 50 μm and 85 μm in living mouse bone marrow respectively, allowing us to characterize mitochondrial health and the survival of functioning cells with a field of view of 67.5× 67.5 μm. We also investigate the role of initial signal and background levels in sample correction quality by varying the laser power and camera exposure time and develop an intensity-based criteria for sample correction.
Discussion: This study demonstrates a promising tool for imaging of mitochondria and other organelles in optically distorting biological environments, which could facilitate the study of a variety of diseases connected to mitochondrial morphology and activity in a range of biological tissues.
Background: Abnormalities in brain regions involved in the pathophysiology of schizophrenia (SCZ) may present insight into individual clinical symptoms. Specifically, functional connectivity irregularities may provide potential biomarkers for treatment response or treatment resistance, as such changes can occur before any structural changes are visible. We reviewed resting-state functional magnetic resonance imaging (rs-fMRI) findings from the last decade to provide an overview of the current knowledge on brain functional connectivity abnormalities and their associations to symptoms in treatment-resistant schizophrenia (TRS) and ultra-treatment-resistant schizophrenia (UTRS) and to look for support for the dysconnection hypothesis.
Methods: PubMed database was searched for articles published in the last 10 years applying rs-fMRI in TRS patients, i.e., who had not responded to at least two adequate treatment trials with different antipsychotic drugs.
Results: Eighteen articles were selected for this review involving 648 participants (TRS and control cohorts). The studies showed frontal hypoconnectivity before the initiation of treatment with CLZ or riluzole, an increase in frontal connectivity after riluzole treatment, fronto-temporal hypoconnectivity that may be specific for non-responders, widespread abnormal connectivity during mixed treatments, and ECT-induced effects on the limbic system.
Conclusion: Probably due to the heterogeneity in the patient cohorts concerning antipsychotic treatment and other clinical variables (e.g., treatment response, lifetime antipsychotic drug exposure, duration of illness, treatment adherence), widespread abnormalities in connectivity were noted. However, irregularities in frontal brain regions, especially in the prefrontal cortex, were noted which are consistent with previous SCZ literature and the dysconnectivity hypothesis. There were major limitations, as most studies did not differentiate between TRS and UTRS (i.e., CLZ-resistant schizophrenia) and investigated heterogeneous cohorts treated with mixed treatments (with or without CLZ). This is critical as in different subtypes of the disorder an interplay between dopaminergic and glutamatergic pathways involving frontal, striatal, and hippocampal brain regions in separate ways is likely. Better definitions of TRS and UTRS are necessary in future longitudinal studies to correctly differentiate brain regions underlying the pathophysiology of SCZ, which could serve as potential functional biomarkers for treatment resistance.
Transcranial electrical stimulation (tES) technology and neuroimaging are increasingly coupled in basic and applied science. This synergy has enabled individualized tES therapy and facilitated causal inferences in functional neuroimaging. However, traditional tES paradigms have been stymied by relatively small changes in neural activity and high inter-subject variability in cognitive effects. In this perspective, we propose a tES framework to treat these issues which is grounded in dynamical systems and control theory. The proposed paradigm involves a tight coupling of tES and neuroimaging in which M/EEG is used to parameterize generative brain models as well as control tES delivery in a hybrid closed-loop fashion. We also present a novel quantitative framework for cognitive enhancement driven by a new computational objective: shaping how the brain reacts to potential "inputs" (e.g., task contexts) rather than enforcing a fixed pattern of brain activity.