Pub Date : 2023-01-01DOI: 10.3389/fnimg.2023.1147508
Dulal K Bhaumik, Yue Wang, Pei-Shan Yen, Olusola A Ajilore
In this article, we developed a Bayesian multimodal model to detect biomarkers (or neuromarkers) using resting-state functional and structural data while comparing a late-life depression group with a healthy control group. Biomarker detection helps determine a target for treatment intervention to get the optimal therapeutic benefit for treatment-resistant patients. The borrowing strength of the structural connectivity has been quantified for functional activity while detecting the biomarker. In the biomarker searching process, thousands of hypotheses are generated and tested simultaneously using our novel method to control the false discovery rate for small samples. Several existing statistical approaches, frequently used in analyzing neuroimaging data have been investigated and compared via simulation with the proposed approach to show its excellent performance. Results are illustrated with a live data set generated in a late-life depression study. The role of detected biomarkers in terms of cognitive function has been explored.
{"title":"Development of a Bayesian multimodal model to detect biomarkers in neuroimaging studies.","authors":"Dulal K Bhaumik, Yue Wang, Pei-Shan Yen, Olusola A Ajilore","doi":"10.3389/fnimg.2023.1147508","DOIUrl":"https://doi.org/10.3389/fnimg.2023.1147508","url":null,"abstract":"<p><p>In this article, we developed a Bayesian multimodal model to detect biomarkers (or neuromarkers) using resting-state functional and structural data while comparing a late-life depression group with a healthy control group. Biomarker detection helps determine a target for treatment intervention to get the optimal therapeutic benefit for treatment-resistant patients. The borrowing strength of the structural connectivity has been quantified for functional activity while detecting the biomarker. In the biomarker searching process, thousands of hypotheses are generated and tested simultaneously using our novel method to control the false discovery rate for small samples. Several existing statistical approaches, frequently used in analyzing neuroimaging data have been investigated and compared via simulation with the proposed approach to show its excellent performance. Results are illustrated with a live data set generated in a late-life depression study. The role of detected biomarkers in terms of cognitive function has been explored.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"2 ","pages":"1147508"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9963087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnimg.2023.1129587
Emily Anne Robinson, John Gleeson, Arush Honnedevasthana Arun, Adam Clemente, Alexandra Gaillard, Maria Gloria Rossetti, Paolo Brambilla, Marcella Bellani, Camilla Crisanti, H Valerie Curran, Valentina Lorenzetti
Introduction: Cannabis is the most widely used regulated substance by youth and adults. Cannabis use has been associated with psychosocial problems, which have been partly ascribed to neurobiological changes. Emerging evidence to date from diffusion-MRI studies shows that cannabis users compared to controls show poorer integrity of white matter fibre tracts, which structurally connect distinct brain regions to facilitate neural communication. However, the most recent evidence from diffusion-MRI studies thus far has yet to be integrated. Therefore, it is unclear if white matter differences in cannabis users are evident consistently in selected locations, in specific diffusion-MRI metrics, and whether these differences in metrics are associated with cannabis exposure levels.
Methods: We systematically reviewed the results from diffusion-MRI imaging studies that compared white matter differences between cannabis users and controls. We also examined the associations between cannabis exposure and other behavioral variables due to changes in white matter. Our review was pre-registered in PROSPERO (ID: 258250; https://www.crd.york.ac.uk/prospero/).
Results: We identified 30 diffusion-MRI studies including 1,457 cannabis users and 1,441 controls aged 16-to-45 years. All but 6 studies reported group differences in white matter integrity. The most consistent differences between cannabis users and controls were lower fractional anisotropy within the arcuate/superior longitudinal fasciculus (7 studies), and lower fractional anisotropy of the corpus callosum (6 studies) as well as higher mean diffusivity and trace (4 studies). Differences in fractional anisotropy were associated with cannabis use onset (4 studies), especially in the corpus callosum (3 studies).
Discussion: The mechanisms underscoring white matter differences are unclear, and they may include effects of cannabis use onset during youth, neurotoxic effects or neuro adaptations from regular exposure to tetrahydrocannabinol (THC), which exerts its effects by binding to brain receptors, or a neurobiological vulnerability predating the onset of cannabis use. Future multimodal neuroimaging studies, including recently developed advanced diffusion-MRI metrics, can be used to track cannabis users over time and to define with precision when and which region of the brain the white matter changes commence in youth cannabis users, and whether cessation of use recovers white matter differences.
{"title":"Measuring white matter microstructure in 1,457 cannabis users and 1,441 controls: A systematic review of diffusion-weighted MRI studies.","authors":"Emily Anne Robinson, John Gleeson, Arush Honnedevasthana Arun, Adam Clemente, Alexandra Gaillard, Maria Gloria Rossetti, Paolo Brambilla, Marcella Bellani, Camilla Crisanti, H Valerie Curran, Valentina Lorenzetti","doi":"10.3389/fnimg.2023.1129587","DOIUrl":"https://doi.org/10.3389/fnimg.2023.1129587","url":null,"abstract":"<p><strong>Introduction: </strong>Cannabis is the most widely used regulated substance by youth and adults. Cannabis use has been associated with psychosocial problems, which have been partly ascribed to neurobiological changes. Emerging evidence to date from diffusion-MRI studies shows that cannabis users compared to controls show poorer integrity of white matter fibre tracts, which structurally connect distinct brain regions to facilitate neural communication. However, the most recent evidence from diffusion-MRI studies thus far has yet to be integrated. Therefore, it is unclear if white matter differences in cannabis users are evident consistently in selected locations, in specific diffusion-MRI metrics, and whether these differences in metrics are associated with cannabis exposure levels.</p><p><strong>Methods: </strong>We systematically reviewed the results from diffusion-MRI imaging studies that compared white matter differences between cannabis users and controls. We also examined the associations between cannabis exposure and other behavioral variables due to changes in white matter. Our review was pre-registered in PROSPERO (ID: 258250; https://www.crd.york.ac.uk/prospero/).</p><p><strong>Results: </strong>We identified 30 diffusion-MRI studies including 1,457 cannabis users and 1,441 controls aged 16-to-45 years. All but 6 studies reported group differences in white matter integrity. The most consistent differences between cannabis users and controls were lower fractional anisotropy within the arcuate/superior longitudinal fasciculus (7 studies), and lower fractional anisotropy of the corpus callosum (6 studies) as well as higher mean diffusivity and trace (4 studies). Differences in fractional anisotropy were associated with cannabis use onset (4 studies), especially in the corpus callosum (3 studies).</p><p><strong>Discussion: </strong>The mechanisms underscoring white matter differences are unclear, and they may include effects of cannabis use onset during youth, neurotoxic effects or neuro adaptations from regular exposure to tetrahydrocannabinol (THC), which exerts its effects by binding to brain receptors, or a neurobiological vulnerability predating the onset of cannabis use. Future multimodal neuroimaging studies, including recently developed advanced diffusion-MRI metrics, can be used to track cannabis users over time and to define with precision when and which region of the brain the white matter changes commence in youth cannabis users, and whether cessation of use recovers white matter differences.</p><p><strong>Systematic review registration: </strong>www.crd.york.ac.uk/prospero/, identifier: 258250.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"2 ","pages":"1129587"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10319559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnimg.2023.1119539
Vismay Agrawal, Xiaole Z Zhong, J Jean Chen
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.
{"title":"Generating dynamic carbon-dioxide traces from respiration-belt recordings: Feasibility using neural networks and application in functional magnetic resonance imaging.","authors":"Vismay Agrawal, Xiaole Z Zhong, J Jean Chen","doi":"10.3389/fnimg.2023.1119539","DOIUrl":"https://doi.org/10.3389/fnimg.2023.1119539","url":null,"abstract":"<p><strong>Introduction: </strong>In the context of functional magnetic resonance imaging (fMRI), carbon dioxide (CO<sub>2</sub>) is a well-known vasodilator that has been widely used to monitor and interrogate vascular physiology. Moreover, spontaneous fluctuations in end-tidal carbon dioxide (PETCO<sub>2</sub>) reflects changes in arterial CO<sub>2</sub> 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 CO<sub>2</sub> recordings, and most often only heart rate and respiration are recorded. While the intrinsic link between these latter metrics and CO<sub>2</sub> led to suggested possible analytical models, they have not been widely applied.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>We demonstrate that the one-to-one mapping between respiration and CO<sub>2</sub> 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 CO<sub>2</sub>. Moreover, dynamic PETCO<sub>2</sub> can be successfully derived from the predicted CO<sub>2</sub>, 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 CO<sub>2</sub> prediction.</p><p><strong>Discussion: </strong>Our results demonstrate that dynamic CO<sub>2</sub> 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.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"2 ","pages":"1119539"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9956737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnimg.2023.1055463
Elisa Moya-Sáez, Rodrigo de Luis-García, Carlos Alberola-López
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.
{"title":"Toward deep learning replacement of gadolinium in neuro-oncology: A review of contrast-enhanced synthetic MRI.","authors":"Elisa Moya-Sáez, Rodrigo de Luis-García, Carlos Alberola-López","doi":"10.3389/fnimg.2023.1055463","DOIUrl":"https://doi.org/10.3389/fnimg.2023.1055463","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"2 ","pages":"1055463"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10337585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnimg.2023.1109546
Anish V Sathe, Caio M Matias, Michael Kogan, Isaiah Ailes, Mashaal Syed, KiChang Kang, Jingya Miao, Kiran Talekar, Scott Faro, Feroze B Mohamed, Joseph Tracy, Ashwini Sharan, Mahdi Alizadeh
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.
{"title":"Resting-State fMRI Can Detect Alterations in Seizure Onset and Spread Regions in Patients with Non-Lesional Epilepsy: A Pilot Study.","authors":"Anish V Sathe, Caio M Matias, Michael Kogan, Isaiah Ailes, Mashaal Syed, KiChang Kang, Jingya Miao, Kiran Talekar, Scott Faro, Feroze B Mohamed, Joseph Tracy, Ashwini Sharan, Mahdi Alizadeh","doi":"10.3389/fnimg.2023.1109546","DOIUrl":"https://doi.org/10.3389/fnimg.2023.1109546","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10194331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9496973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnimg.2023.1158159
Nina Purg, Jure Demšar, Alan Anticevic, Grega Repovš
[This corrects the article DOI: 10.3389/fnimg.2022.983324.].
[这更正了文章DOI: 10.3389/fnimg.2022.983324.]。
{"title":"Corrigendum: autohrf-an R package for generating data-informed event models for general linear modeling of task-based fMRI data.","authors":"Nina Purg, Jure Demšar, Alan Anticevic, Grega Repovš","doi":"10.3389/fnimg.2023.1158159","DOIUrl":"https://doi.org/10.3389/fnimg.2023.1158159","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnimg.2022.983324.].</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"2 ","pages":"1158159"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10332277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnimg.2023.959601
Tianyi Zheng, Adrian R Liversage, Kayvan F Tehrani, Jarrod A Call, Peter A Kner, Luke J Mortensen
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.
{"title":"Imaging mitochondria through bone in live mice using two-photon fluorescence microscopy with adaptive optics.","authors":"Tianyi Zheng, Adrian R Liversage, Kayvan F Tehrani, Jarrod A Call, Peter A Kner, Luke J Mortensen","doi":"10.3389/fnimg.2023.959601","DOIUrl":"https://doi.org/10.3389/fnimg.2023.959601","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"2 ","pages":"959601"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9963088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnimg.2023.1127508
Noora Tuovinen, Alex Hofer
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.
{"title":"Resting-state functional MRI in treatment-resistant schizophrenia.","authors":"Noora Tuovinen, Alex Hofer","doi":"10.3389/fnimg.2023.1127508","DOIUrl":"https://doi.org/10.3389/fnimg.2023.1127508","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"2 ","pages":"1127508"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9956741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}