Wenshen Wang, Jiadi Xu, Aline M. Thomas, Guanshu Liu
INTRODUCTION: The blood-brain barrier (BBB) is compromised in multiple central nervous system (CNS) disorders associated with neuroinflammation, including multiple sclerosis (MS). Currently available magnetic resonance imaging (MRI) methods, however, are only able to measure BBB leakage in the lower molecular size range with the use of small molecular tracers, i.e., gadolinium (Gd) agents (<1 kDa)1,2 and water (18 Da).3,4 The goal of this study is to adopt a dextran-based chemical exchange saturation transfer (CEST) MRI approach for assessing BBB leakage in the larger size range and studying the size characteristics of BBB dysfunction. METHODS: All animal experiments will be approved by the Animal Care and Use Committee of Johns Hopkins University. EAE MS mouse model: C57Bl/6 mice (F/6-10w), were injected s.c. with myelin peptide (MOG35-55, 200 μL, 0.5 mg/mL) emulsified in incomplete Freund's adjuvant supplemented with M. tuberculosis H37Ra (5 mg/mL) and i.p. with 300 ng of pertussis toxin on days 0 and 2. Mice were observed daily for signs of paralysis using a 0-5 rating system. Fluorescent imaging. EAE mice (n=3) were injected with the combination of fixable Dex40-TRITC and Dex3-FITC (i.v.) at the dose of 80 mg/kg, and sacrificed at 30 min after injection (without perfusion) to collect brains. Fluorescence microscopy was then performed on tissue sections. MRI: all in vivo MRI was acquired using a Biospec 11.7 T horizontal MRI scanner (Bruker, Ettlingen, Germany). According to our previously reported protocol,5 CEST MRI was performed before and after the i.v. injection of 200 µL dex40 saline solution (750 mg/kg b.w), using parameters: B1=1.8 µT, Tsat=3 s, Δω=-3 to +3 ppm with a step size of 0.2 ppm. MTRasym=(S-Δω–S+Δω)/S0 was computed after the B0 correction using the WASSR method. ΔMTRasym (1 ppm) at each time point was calculated by MTRasym (t)- MTRasym (pre). RESULTS: 1. The size-dependent BBB disruption in MS can be detected by fluorescent dextran-tracers of different sizes: Immunofluorescent results show dextrans of smaller sizes (e.g., 3 kDa) penetrated the brain parenchyma deeper than larger sizes (e.g., 40 kDa). Our study proves the feasibility to use dextrans as a group of tracers with different sizes for probing the size effect of BBB dysfunction. 2. Dex-enhanced CEST MRI: As shown in Figure 1, mice with high clinical disability scores have BBB impairment in the mouse brain, confirmed with Gd-enhanced MRI (Figure 1B). Dex-enhanced MRI results (Figure 1C) showed substantial contrast enhancement in the corresponding brain regions. Interestingly, while the size of Dex (40 kDa) is larger than the size of Gd-DOTA (559 Da), the area showing enhanced Dex-CEST signal is slightly larger than that of Gd-enhancement, suggesting that, besides size, other particle properties such as shape and surface properties of a given agent/particle may also contribute to the permeation across BBB. CONCLUSIONS: We have established a dextran-based imaging pro
{"title":"Dextran-enhanced CEST MRI reveals the size effect of BBB dysfunction associated with neuroinflammation","authors":"Wenshen Wang, Jiadi Xu, Aline M. Thomas, Guanshu Liu","doi":"10.4081/vl.2022.10960","DOIUrl":"https://doi.org/10.4081/vl.2022.10960","url":null,"abstract":"INTRODUCTION: The blood-brain barrier (BBB) is compromised in multiple central nervous system (CNS) disorders associated with neuroinflammation, including multiple sclerosis (MS). Currently available magnetic resonance imaging (MRI) methods, however, are only able to measure BBB leakage in the lower molecular size range with the use of small molecular tracers, i.e., gadolinium (Gd) agents (<1 kDa)1,2 and water (18 Da).3,4 The goal of this study is to adopt a dextran-based chemical exchange saturation transfer (CEST) MRI approach for assessing BBB leakage in the larger size range and studying the size characteristics of BBB dysfunction. \u0000METHODS: All animal experiments will be approved by the Animal Care and Use Committee of Johns Hopkins University. EAE MS mouse model: C57Bl/6 mice (F/6-10w), were injected s.c. with myelin peptide (MOG35-55, 200 μL, 0.5 mg/mL) emulsified in incomplete Freund's adjuvant supplemented with M. tuberculosis H37Ra (5 mg/mL) and i.p. with 300 ng of pertussis toxin on days 0 and 2. Mice were observed daily for signs of paralysis using a 0-5 rating system. Fluorescent imaging. EAE mice (n=3) were injected with the combination of fixable Dex40-TRITC and Dex3-FITC (i.v.) at the dose of 80 mg/kg, and sacrificed at 30 min after injection (without perfusion) to collect brains. Fluorescence microscopy was then performed on tissue sections. MRI: all in vivo MRI was acquired using a Biospec 11.7 T horizontal MRI scanner (Bruker, Ettlingen, Germany). According to our previously reported protocol,5 CEST MRI was performed before and after the i.v. injection of 200 µL dex40 saline solution (750 mg/kg b.w), using parameters: B1=1.8 µT, Tsat=3 s, Δω=-3 to +3 ppm with a step size of 0.2 ppm. MTRasym=(S-Δω–S+Δω)/S0 was computed after the B0 correction using the WASSR method. ΔMTRasym (1 ppm) at each time point was calculated by MTRasym (t)- MTRasym (pre). \u0000RESULTS: 1. The size-dependent BBB disruption in MS can be detected by fluorescent dextran-tracers of different sizes: Immunofluorescent results show dextrans of smaller sizes (e.g., 3 kDa) penetrated the brain parenchyma deeper than larger sizes (e.g., 40 kDa). Our study proves the feasibility to use dextrans as a group of tracers with different sizes for probing the size effect of BBB dysfunction. 2. Dex-enhanced CEST MRI: As shown in Figure 1, mice with high clinical disability scores have BBB impairment in the mouse brain, confirmed with Gd-enhanced MRI (Figure 1B). Dex-enhanced MRI results (Figure 1C) showed substantial contrast enhancement in the corresponding brain regions. Interestingly, while the size of Dex (40 kDa) is larger than the size of Gd-DOTA (559 Da), the area showing enhanced Dex-CEST signal is slightly larger than that of Gd-enhancement, suggesting that, besides size, other particle properties such as shape and surface properties of a given agent/particle may also contribute to the permeation across BBB. \u0000CONCLUSIONS: We have established a dextran-based imaging pro","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122838722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Shaykevich, Russell W. Chan, Chandni Rana, M. Eltaeb, J. P. Little, D. Razansky, Kevin C. Chan, S. Shoham
Background: The glymphatic system is a brain waste clearance system mediated via cerebrospinal fluid (CSF) flow,1 with implications for influence on neurodegenerative diseases.2 Most preclinical glymphatic studies employ fluorescence imaging, which provides higher specificity, but a smaller field-of-view (FOV), or magnetic resonance imaging (MRI), which provides brain-wide FOV, but lower specificity. Functional optoacoustic neuro-tomography3 (FONT) offers a larger FOV compared to classical optical methods, and higher specificity compared to MRI. However, FONT has not yet been applied to probe the glymphatic system. In this study, we used fluorescence and optoacoustic imaging of a near-infrared dye, Janelia Fluor 669 (JF669), to track CSF and multimodal CSF-hemodynamic flows in mice. Methods: After observing strong fluorescence and optoacoustic signatures of JF669 in phantom experiments, we performed a series of in vivo experiments in isoflurane-anesthetized C57BL/6 mice (n=3 fluorescence and n=4 FONT experiments, respectively) (Figure 1A). The lumbar injection was applied to deliver JF669 at a rate of 2 µL/min for 30 minutes. A polyethylene tube was placed intrathecally at the lumbar region (L4-L5). The scalp was removed. Fluorescence or FONT images were obtained every 5 minutes after injection. Results: Fluorescence imaging and FONT probe CSF flow Images (Figure 1B) and time traces (Figure 1C) revealed time-dependent anatomical routes of paravascular influx, including the transport along the olfactory artery (OFA), superior cerebellar artery (SCA), and bilateral middle cerebral artery (MCA). For FONT imaging, since the OFA showed strong fluorescence (Figure 1B), we positioned the ultrasound transducer array at the anterior of the mouse brain with a FOV of 5x5 mm2 (Figure 1A). Standard filtered back-projection reconstruction was applied. Besides the OFA route of the paravascular influx, the dynamic images (Figure 1D) and time-traces (Figure 1E) also revealed time-dependent anatomical routes of CSF-interstitial fluid (ISF) exchange in the olfactory bulb (OFB) and paravascular efflux in the superior sagittal sinus (SSS) and the bilateral inferior cerebral vein (ICV). Next, we studied the aquaporin-4 (AQP4) dependence of glymphatic flow by subcutaneously injecting AQP4 inhibitor TGN020, in addition to the prior procedures. Under fluorescence imaging and FONT, we observed that TGN020 significantly decreased and spatially restricted the spread of JF669 in the brain. FONT spectral unmixing separates CSF and blood We swept the OPO through 680 nm to 750 nm, with 10 nm steps at 10 Hz in the phantom and in each animal. The multispectral reconstructions were unmixed using the known absorption spectra of hemoglobin and the JF669 OA spectrum obtained from the phantom.4 This enabled the separation of blood and JF669 signal (Figure 1D). Conclusions: We characterized anatomical routes of paravascular influx (OFA), CSF-ISF exchange (OFB) and paravascular efflu
{"title":"Optoacoustic imaging of the glymphatic system","authors":"Sarah Shaykevich, Russell W. Chan, Chandni Rana, M. Eltaeb, J. P. Little, D. Razansky, Kevin C. Chan, S. Shoham","doi":"10.4081/vl.2022.10967","DOIUrl":"https://doi.org/10.4081/vl.2022.10967","url":null,"abstract":"Background: The glymphatic system is a brain waste clearance system mediated via cerebrospinal fluid (CSF) flow,1 with implications for influence on neurodegenerative diseases.2 Most preclinical glymphatic studies employ fluorescence imaging, which provides higher specificity, but a smaller field-of-view (FOV), or magnetic resonance imaging (MRI), which provides brain-wide FOV, but lower specificity. Functional optoacoustic neuro-tomography3 (FONT) offers a larger FOV compared to classical optical methods, and higher specificity compared to MRI. However, FONT has not yet been applied to probe the glymphatic system. In this study, we used fluorescence and optoacoustic imaging of a near-infrared dye, Janelia Fluor 669 (JF669), to track CSF and multimodal CSF-hemodynamic flows in mice. \u0000Methods: After observing strong fluorescence and optoacoustic signatures of JF669 in phantom experiments, we performed a series of in vivo experiments in isoflurane-anesthetized C57BL/6 mice (n=3 fluorescence and n=4 FONT experiments, respectively) (Figure 1A). The lumbar injection was applied to deliver JF669 at a rate of 2 µL/min for 30 minutes. A polyethylene tube was placed intrathecally at the lumbar region (L4-L5). The scalp was removed. Fluorescence or FONT images were obtained every 5 minutes after injection. \u0000Results: Fluorescence imaging and FONT probe CSF flow Images (Figure 1B) and time traces (Figure 1C) revealed time-dependent anatomical routes of paravascular influx, including the transport along the olfactory artery (OFA), superior cerebellar artery (SCA), and bilateral middle cerebral artery (MCA). For FONT imaging, since the OFA showed strong fluorescence (Figure 1B), we positioned the ultrasound transducer array at the anterior of the mouse brain with a FOV of 5x5 mm2 (Figure 1A). Standard filtered back-projection reconstruction was applied. Besides the OFA route of the paravascular influx, the dynamic images (Figure 1D) and time-traces (Figure 1E) also revealed time-dependent anatomical routes of CSF-interstitial fluid (ISF) exchange in the olfactory bulb (OFB) and paravascular efflux in the superior sagittal sinus (SSS) and the bilateral inferior cerebral vein (ICV). Next, we studied the aquaporin-4 (AQP4) dependence of glymphatic flow by subcutaneously injecting AQP4 inhibitor TGN020, in addition to the prior procedures. Under fluorescence imaging and FONT, we observed that TGN020 significantly decreased and spatially restricted the spread of JF669 in the brain. FONT spectral unmixing separates CSF and blood We swept the OPO through 680 nm to 750 nm, with 10 nm steps at 10 Hz in the phantom and in each animal. The multispectral reconstructions were unmixed using the known absorption spectra of hemoglobin and the JF669 OA spectrum obtained from the phantom.4 This enabled the separation of blood and JF669 signal (Figure 1D). \u0000Conclusions: We characterized anatomical routes of paravascular influx (OFA), CSF-ISF exchange (OFB) and paravascular efflu","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124603771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain function requires a finely regulated balance between the delivery of nutrients and the clearance of waste products through the blood flow.1 If the blood flow delivery does not match the dynamic requirements for oxygen and glucose imposed by neural activity, brain dysfunction and damage may ensue. The cognitive alterations caused by vascular factors (vascular cognitive impairment, VCI) and neurodegeneration (Alzheimer’s disease, AD) have traditionally been considered mechanistically distinct, but increasing evidence suggests previously unappreciated commonalities.2 Clinical-pathological studies indicate that vascular lesions aggravate the deleterious effects of AD pathology and traditional stroke risk factors, such as hypertension, are also risk factors for AD, suggesting mechanistic overlap. Furthermore, disturbances of cerebral perfusion and/or energy metabolism occur early in the clinical course of AD suggesting a pathogenic role of vascular insufficiency.3 Corroborating this clinical-epidemiological evidence, experimental data indicate that amyloid-beta, a key pathogenic factor in AD, alters the structure and function of cerebral blood vessels and associated cells (neurovascular complex), effects mediated by activation of innate immune cells leading to vascular oxidative stress and inflammation.1 On the other hand, pathological tau suppresses glutamate-dependent production of nitric oxide, which, in turn, dampens the increase in blood flow produced by synaptic activity, but also leads to neuronal network dysfunction and increased excitability.4 Aging and hypertension can also influence the production and clearance of amyloid-beta, promoting amyloid pathology. Furthermore, ApoE4 plays a critical role in the brain’s susceptibility to vascular damage or neurodegeneration.5 Injury to the neurovascular complex alters cerebral blood flow regulation, depletes vascular reserves, and reduces the brain’s repair potential, effects that amplify the brain dysfunction and damage exerted by incident ischemia and coexisting neurodegeneration. These observations, collectively, indicate that vascular alterations are important both in vascular and neurodegenerative dementias, and suggest novel preventive and treatment modalities for these devastating and highly prevalent conditions. Therefore, in the absence of mechanism-based approaches to counteract dementia, targeting cerebrovascular function may offer the opportunity to mitigate the public health impact of one of the most disabling human afflictions.
{"title":"Neurovascular risk factors and dysfunction in aging and dementia","authors":"C. Iadecola","doi":"10.4081/vl.2022.10951","DOIUrl":"https://doi.org/10.4081/vl.2022.10951","url":null,"abstract":"Brain function requires a finely regulated balance between the delivery of nutrients and the clearance of waste products through the blood flow.1 If the blood flow delivery does not match the dynamic requirements for oxygen and glucose imposed by neural activity, brain dysfunction and damage may ensue. The cognitive alterations caused by vascular factors (vascular cognitive impairment, VCI) and neurodegeneration (Alzheimer’s disease, AD) have traditionally been considered mechanistically distinct, but increasing evidence suggests previously unappreciated commonalities.2 Clinical-pathological studies indicate that vascular lesions aggravate the deleterious effects of AD pathology and traditional stroke risk factors, such as hypertension, are also risk factors for AD, suggesting mechanistic overlap. Furthermore, disturbances of cerebral perfusion and/or energy metabolism occur early in the clinical course of AD suggesting a pathogenic role of vascular insufficiency.3 Corroborating this clinical-epidemiological evidence, experimental data indicate that amyloid-beta, a key pathogenic factor in AD, alters the structure and function of cerebral blood vessels and associated cells (neurovascular complex), effects mediated by activation of innate immune cells leading to vascular oxidative stress and inflammation.1 On the other hand, pathological tau suppresses glutamate-dependent production of nitric oxide, which, in turn, dampens the increase in blood flow produced by synaptic activity, but also leads to neuronal network dysfunction and increased excitability.4 Aging and hypertension can also influence the production and clearance of amyloid-beta, promoting amyloid pathology. Furthermore, ApoE4 plays a critical role in the brain’s susceptibility to vascular damage or neurodegeneration.5 Injury to the neurovascular complex alters cerebral blood flow regulation, depletes vascular reserves, and reduces the brain’s repair potential, effects that amplify the brain dysfunction and damage exerted by incident ischemia and coexisting neurodegeneration. These observations, collectively, indicate that vascular alterations are important both in vascular and neurodegenerative dementias, and suggest novel preventive and treatment modalities for these devastating and highly prevalent conditions. Therefore, in the absence of mechanism-based approaches to counteract dementia, targeting cerebrovascular function may offer the opportunity to mitigate the public health impact of one of the most disabling human afflictions.","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"191 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132865577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background. The growing interest in the brain clearance system in the last decade has led to great insights into how waste clearance via perivascular spaces acts like a lymphatic-like system. However, most of these observations have been done in rodent studies, often with invasive techniques. When aiming to understand the human brain clearance system, the main technology has so far relied on intrathecal injections1 and cerebrospinal fluid (CSF) flow in larger structures like the fourth ventricle2 or the aqueduct. The availability of non-invasive imaging technology would be an important driver to probe human brain clearance in health and disease. Methods. When looking at the current knowledge on brain clearance, it is clear that CSF and interstitial fluid (ISF) are the main solvents that propel waste out of the brain. The insight that CSF and ISF mainly consist of water makes magnetic resonance imaging (MRI) an attractive modality, since many possibilities exist to measure cerebral water dynamics, such as transitions between compartments, as well as water flow/diffusion in sub-compartments. MRI does provide excellent opportunities to image CSF/ISF, due to the long T2 of these compared to background tissue. By using long echo-time imaging, MRI sequences can be tuned towards CSF and ISF. This approach is applied both to arterial spin labeling (ASL) MRI to measure water transport across the blood-CSF barrier, as well as to high spatial resolution imaging at 7 tesla MRI to measure CSF mobility in perivascular spaces. Results. By using ASL that magnetically labels inflowing blood, we could prove that water exchange into CSF is not only taking place in the choroid plexus, but also in the subarachnoid space.3 We refer to the reference for a complete description of the method and results.3 The second technique also exploits long echo times to isolate CSF-signal, but combines this with high spatial resolution readouts and motion-sensitizing gradients to allow measurement of the CSF-mobility in the perivascular spaces of penetrating arteries (Figure 1) and e.g. the subarachnoid space around the MCA. Retrospective triggering allows studying how the cardiac and respiratory cycle influence the CSF-mobility, i.e. the driving forces of propulsion and mixing processes within the perivascular spaces (PVS). Preliminary results show approximately equal contributions from the cardiac and respiratory cycles in smaller PVS.4 Conclusions The exchange of water between the vascular and CSF compartments does not exclusively happen in the choroid plexus, but also in the subarachnoid arteries along the cortex. CSF mobility is influenced both by cardiac and respiratory cycles in approximately equal contributions in the PVS of penetrating arteries.
{"title":"Probing cerebrospinal fluid mobility for human brain clearance imaging MRI: water transport across the blood-cerebrospinal fluid barrier and mobility of cerebrospinal fluid in perivascular spaces","authors":"M. V. van Osch, L. Petitclerc, Lydiane Hirschler","doi":"10.4081/vl.2022.10942","DOIUrl":"https://doi.org/10.4081/vl.2022.10942","url":null,"abstract":"Background. The growing interest in the brain clearance system in the last decade has led to great insights into how waste clearance via perivascular spaces acts like a lymphatic-like system. However, most of these observations have been done in rodent studies, often with invasive techniques. When aiming to understand the human brain clearance system, the main technology has so far relied on intrathecal injections1 and cerebrospinal fluid (CSF) flow in larger structures like the fourth ventricle2 or the aqueduct. The availability of non-invasive imaging technology would be an important driver to probe human brain clearance in health and disease. \u0000Methods. When looking at the current knowledge on brain clearance, it is clear that CSF and interstitial fluid (ISF) are the main solvents that propel waste out of the brain. The insight that CSF and ISF mainly consist of water makes magnetic resonance imaging (MRI) an attractive modality, since many possibilities exist to measure cerebral water dynamics, such as transitions between compartments, as well as water flow/diffusion in sub-compartments. MRI does provide excellent opportunities to image CSF/ISF, due to the long T2 of these compared to background tissue. By using long echo-time imaging, MRI sequences can be tuned towards CSF and ISF. This approach is applied both to arterial spin labeling (ASL) MRI to measure water transport across the blood-CSF barrier, as well as to high spatial resolution imaging at 7 tesla MRI to measure CSF mobility in perivascular spaces. \u0000Results. By using ASL that magnetically labels inflowing blood, we could prove that water exchange into CSF is not only taking place in the choroid plexus, but also in the subarachnoid space.3 We refer to the reference for a complete description of the method and results.3 The second technique also exploits long echo times to isolate CSF-signal, but combines this with high spatial resolution readouts and motion-sensitizing gradients to allow measurement of the CSF-mobility in the perivascular spaces of penetrating arteries (Figure 1) and e.g. the subarachnoid space around the MCA. Retrospective triggering allows studying how the cardiac and respiratory cycle influence the CSF-mobility, i.e. the driving forces of propulsion and mixing processes within the perivascular spaces (PVS). Preliminary results show approximately equal contributions from the cardiac and respiratory cycles in smaller PVS.4 Conclusions The exchange of water between the vascular and CSF compartments does not exclusively happen in the choroid plexus, but also in the subarachnoid arteries along the cortex. CSF mobility is influenced both by cardiac and respiratory cycles in approximately equal contributions in the PVS of penetrating arteries.","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125008509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Chawla, G. Verma, Ravi Prakash Reddy Nanga, S. Mohan, Harish Poptani
Proton magnetic resonance spectroscopy (1H-MRS) allows non-invasive assessment of the metabolic landscape of biological tissue. Despite demonstrating promising findings in clinical practice, single-voxel or single-slice two-dimensional 1H-MRS methods present a few challenges mainly related to limited spatial coverage and low spatial and spectral resolutions. In the recent past, the advent of more sophisticated metabolic imaging and spectroscopic sequences, such as three-dimensional echoplanar spectroscopic imaging (3D-EPSI), two-dimensional correlation spectroscopy (2D-COSY), and chemical exchange saturation technique (CEST) has revolutionized the field of metabolomics. For the metabolic characterization of diffused neurodegenerative diseases, whole brain coverage is essential for a comprehensive overview of the topography and understanding of the underlying pathophysiological processes. The 3D-EPSI sequence allows the acquisition of whole brain (volumetric) metabolite maps with high spatial resolution.1 These metabolite maps can be co-registered to anatomical images for facilitating the mapping of metabolite alterations from different brain regions in a single session, thus providing the true spatial extent of a global disease. The potential of 3D‐EPSI in characterizing several neurological and neurodegenerative disorders has been reported. On conventional one-dimensional 1H-MRS, spectral peaks due to methyl, methylene, and methine protons from N-acetyl aspartate, glutamate, glutamine, gamma-aminobutyric acid, and taurine extensively overlap in the spectral region of 2-4 ppm, often confounding the reliable detection and quantification of these metabolites. In contrast, 2D-COSY offers unambiguous identification of potentially overlapping resonances by dispersing the multiplet structure of scalar (J)-coupled spin systems into a second spectral dimension,2 especially at higher field strength3,4 and by exploiting the unlikely possibility that two metabolites would share identical chemical shifts in two-dimensions. Due to technical limitations and long acquisition time, 2D-COSY sequence has not been widely used to study neurodegenerative diseases. However, future modifications would benefit from implementing faster acquisition schemes and improved spectral fitting methods for data analysis. We believe that these new approaches could make the clinical applications of the 2D-COSY sequence faster, easier, and more versatile. CEST is a relatively novel metabolic imaging modality that allows the detection of specific exogenous and endogenous metabolites/molecules present at millimolar concentrations. Exchangeable solute protons present in chemical functional groups such as amide (-CONH), amine (-NH2) or hydroxyl (-OH) resonate at a frequency different from bulk water protons. These labile protons are selectively saturated using radiofrequency irradiation, which is subsequently transferred to the bulk water pool, leading to a decrease in the water signal i
{"title":"Emerging metabolic imaging and spectroscopic methods to study neurodegenerative diseases","authors":"S. Chawla, G. Verma, Ravi Prakash Reddy Nanga, S. Mohan, Harish Poptani","doi":"10.4081/vl.2022.10946","DOIUrl":"https://doi.org/10.4081/vl.2022.10946","url":null,"abstract":"Proton magnetic resonance spectroscopy (1H-MRS) allows non-invasive assessment of the metabolic landscape of biological tissue. Despite demonstrating promising findings in clinical practice, single-voxel or single-slice two-dimensional 1H-MRS methods present a few challenges mainly related to limited spatial coverage and low spatial and spectral resolutions. In the recent past, the advent of more sophisticated metabolic imaging and spectroscopic sequences, such as three-dimensional echoplanar spectroscopic imaging (3D-EPSI), two-dimensional correlation spectroscopy (2D-COSY), and chemical exchange saturation technique (CEST) has revolutionized the field of metabolomics. For the metabolic characterization of diffused neurodegenerative diseases, whole brain coverage is essential for a comprehensive overview of the topography and understanding of the underlying pathophysiological processes. The 3D-EPSI sequence allows the acquisition of whole brain (volumetric) metabolite maps with high spatial resolution.1 These metabolite maps can be co-registered to anatomical images for facilitating the mapping of metabolite alterations from different brain regions in a single session, thus providing the true spatial extent of a global disease. The potential of 3D‐EPSI in characterizing several neurological and neurodegenerative disorders has been reported. On conventional one-dimensional 1H-MRS, spectral peaks due to methyl, methylene, and methine protons from N-acetyl aspartate, glutamate, glutamine, gamma-aminobutyric acid, and taurine extensively overlap in the spectral region of 2-4 ppm, often confounding the reliable detection and quantification of these metabolites. In contrast, 2D-COSY offers unambiguous identification of potentially overlapping resonances by dispersing the multiplet structure of scalar (J)-coupled spin systems into a second spectral dimension,2 especially at higher field strength3,4 and by exploiting the unlikely possibility that two metabolites would share identical chemical shifts in two-dimensions. Due to technical limitations and long acquisition time, 2D-COSY sequence has not been widely used to study neurodegenerative diseases. However, future modifications would benefit from implementing faster acquisition schemes and improved spectral fitting methods for data analysis. We believe that these new approaches could make the clinical applications of the 2D-COSY sequence faster, easier, and more versatile. CEST is a relatively novel metabolic imaging modality that allows the detection of specific exogenous and endogenous metabolites/molecules present at millimolar concentrations. Exchangeable solute protons present in chemical functional groups such as amide (-CONH), amine (-NH2) or hydroxyl (-OH) resonate at a frequency different from bulk water protons. These labile protons are selectively saturated using radiofrequency irradiation, which is subsequently transferred to the bulk water pool, leading to a decrease in the water signal i","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"62 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116205400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Chu, Marco Muccio, Brianna E. Damadian, R. Damadian, Y. Ge, M. Gianni, L. Minkoff
Background. Cerebrospinal fluid (CSF) circulation consists of two components, a net flow and a pulsatile flow. CSF is generally believed to be produced through the ventricular choroid plexuses and absorbed in sites such as the subarachnoid granulations and nerve roots, contributing to the net flow. The pulsatile driving forces include cardiac vascular pulsation, respiration and muscular contraction.1 Measuring CSF flow in the upright posture is important because we spend most of our lifetime upright. Methods. Thirty asymptomatic volunteers (age: 22-72; 9 males, 21 females) were scanned in the upright seated and supine position on a 0.6 T multi-position MRI scanner (Fonar, New York, USA). CSF flow and spinal cord pulsation were imaged and quantified at the axial mid-C2 level with cine phase-contrast MRI. Results. In the upright posture, heart rate increased by 10%, and peak CSF diastolic flow decreased by 43% compared to the supine posture.2 In addition, the oscillatory volume of CSF exchanged between the spine and cranium decreased by 37% when going from supine to upright posture, consistent with a previous study.3 This could mean that the amount of time spent in different postures as we age may affect the efficiency of glymphatic brain waste clearance and development of neurodegenerative diseases. A less studied but diagnostically important aspect of CSF flow is the concomitant pulsation of spinal cord and central nervous system (CNS) tissue. For example, it is found that in Alzheimer’s Disease patients, the spinal cord at mid-C2 is pulsating much more in the mid to high frequency range (4 to 8 Hz) compared to normal older people in the supine posture. In the normal population, the mid-C2 spinal cord pulsates much less in the upright posture, with a 40% reduction of peak systolic velocity compared to the supine posture. Other postural differences include the more prominent appearance of nerve roots in the supine posture, shift of venous outflow from jugular veins to epidural/smaller veins, and the slimming of the neck when upright. It is also found that CSF flow is much more sensitive to aging in the upright than in the supine position. More specifically, as we age, heart rate change between postures diminishes and the upright peak systolic/peak-to-peak pressure gradient decreases. Since studies have shown that meditation can slow down brain aging, it would be beneficial to study its effect on CSF flow and the process of brain waste production and clearance. Conclusions. Besides delineating the many significant postural differences in CSF circulation, multi-position CSF imaging is also valuable in diagnosing various diseases such as Chiari malformation,4 Ehlers-Danlos syndrome and tethered cord syndrome in the lumbar spine. Often pathology that is not evident in the traditional supine imaging position can be visualized in other patient positions. Finally, a seminal study5 in rodents found that glymphatic transport is most efficient in the lat
背景。脑脊液(CSF)循环由两部分组成，净流和脉动流。一般认为脑脊液通过脑室脉络膜丛产生，并被蛛网膜下腔颗粒和神经根等部位吸收，形成净血流。脉动驱动力包括心脏血管脉动、呼吸和肌肉收缩测量直立姿势的脑脊液流量很重要，因为我们一生中大部分时间都是直立的。方法。无症状志愿者30名，年龄22-72岁;9名男性，21名女性)在0.6 T多位置MRI扫描仪(Fonar, New York, USA)上以直立坐姿和仰卧位进行扫描。在轴向中c2水平用电影相衬MRI成像和量化脑脊液流量和脊髓搏动。结果。与仰卧位相比，直立体位心率提高10%，脑脊液舒张血流峰值降低43%此外，从仰卧位到直立位时，脊柱和头盖骨之间交换的脑脊液振荡体积减少了37%，这与先前的研究一致这可能意味着，随着年龄的增长，保持不同姿势的时间可能会影响脑淋巴废物清除的效率和神经退行性疾病的发展。脊髓和中枢神经系统(CNS)组织的伴随搏动是脑脊液血流的一个较少研究但诊断上重要的方面。例如，研究发现，与仰卧姿势的正常老年人相比，阿尔茨海默病患者中c2的脊髓在中高频率范围内(4至8赫兹)的脉动要大得多。在正常人群中，直立姿势时中c2脊髓的搏动要少得多，与仰卧姿势相比，峰值收缩速度降低40%。其他体位差异包括仰卧位时更突出的神经根，静脉流出从颈静脉转移到硬膜外静脉/小静脉，直立时颈部变细。我们还发现，与仰卧位相比，直立位的脑脊液流量对衰老更敏感。更具体地说，随着年龄的增长，不同姿势之间的心率变化会减弱，直立峰值收缩压/峰对峰压梯度会减小。由于研究表明冥想可以减缓大脑衰老，因此研究冥想对脑脊液流动和脑废物产生和清除过程的影响将是有益的。结论。除了描绘脑脊液循环中许多重要的体位差异外，多体位脑脊液成像在诊断腰椎Chiari畸形、4 ehers - danlos综合征和脊髓栓系综合征等多种疾病方面也有价值。通常，在传统的仰卧位成像中不明显的病理可以在其他患者的体位中显示出来。最后，一项对啮齿动物的开创性研究发现，与仰卧位或俯卧位相比，侧卧位的淋巴运输效率最高，这表明在未来的诊断成像过程中，评估人类CSF -间质液(ISF)运输时必须考虑姿势。
{"title":"The influence of body position on cerebrospinal fluid circulation","authors":"D. Chu, Marco Muccio, Brianna E. Damadian, R. Damadian, Y. Ge, M. Gianni, L. Minkoff","doi":"10.4081/vl.2022.10947","DOIUrl":"https://doi.org/10.4081/vl.2022.10947","url":null,"abstract":"Background. Cerebrospinal fluid (CSF) circulation consists of two components, a net flow and a pulsatile flow. CSF is generally believed to be produced through the ventricular choroid plexuses and absorbed in sites such as the subarachnoid granulations and nerve roots, contributing to the net flow. The pulsatile driving forces include cardiac vascular pulsation, respiration and muscular contraction.1 Measuring CSF flow in the upright posture is important because we spend most of our lifetime upright. \u0000Methods. Thirty asymptomatic volunteers (age: 22-72; 9 males, 21 females) were scanned in the upright seated and supine position on a 0.6 T multi-position MRI scanner (Fonar, New York, USA). CSF flow and spinal cord pulsation were imaged and quantified at the axial mid-C2 level with cine phase-contrast MRI. \u0000Results. In the upright posture, heart rate increased by 10%, and peak CSF diastolic flow decreased by 43% compared to the supine posture.2 In addition, the oscillatory volume of CSF exchanged between the spine and cranium decreased by 37% when going from supine to upright posture, consistent with a previous study.3 This could mean that the amount of time spent in different postures as we age may affect the efficiency of glymphatic brain waste clearance and development of neurodegenerative diseases. A less studied but diagnostically important aspect of CSF flow is the concomitant pulsation of spinal cord and central nervous system (CNS) tissue. For example, it is found that in Alzheimer’s Disease patients, the spinal cord at mid-C2 is pulsating much more in the mid to high frequency range (4 to 8 Hz) compared to normal older people in the supine posture. In the normal population, the mid-C2 spinal cord pulsates much less in the upright posture, with a 40% reduction of peak systolic velocity compared to the supine posture. Other postural differences include the more prominent appearance of nerve roots in the supine posture, shift of venous outflow from jugular veins to epidural/smaller veins, and the slimming of the neck when upright. It is also found that CSF flow is much more sensitive to aging in the upright than in the supine position. More specifically, as we age, heart rate change between postures diminishes and the upright peak systolic/peak-to-peak pressure gradient decreases. Since studies have shown that meditation can slow down brain aging, it would be beneficial to study its effect on CSF flow and the process of brain waste production and clearance. \u0000Conclusions. Besides delineating the many significant postural differences in CSF circulation, multi-position CSF imaging is also valuable in diagnosing various diseases such as Chiari malformation,4 Ehlers-Danlos syndrome and tethered cord syndrome in the lumbar spine. Often pathology that is not evident in the traditional supine imaging position can be visualized in other patient positions. Finally, a seminal study5 in rodents found that glymphatic transport is most efficient in the lat","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"88 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125086158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: One major thrust in radiology today is image standardization with a focus on rapid, quantitative, multi-contrast data collection and processing. Methods: Strategically acquired gradient echo (STAGE) imaging1-4 is one such method that uses multiple flip angles and multiple echo times. It can provide 8 qualitative and 7 quantitative images as well as transmit field B1 transmit field and B1 receive field maps in 4-6 minutes or less on a 3T magnetic resonance (MR) scanner. STAGE provides qualitative images in the form of proton density-weighted images, T1 weighted images and T2* weighted images. STAGE provides quantitative data in the form of proton spin density (PSD), T1, T2* and susceptibility maps as well as segmentation of white matter, gray matter and cerebrospinal fluid via simulated double inversion recovery (sDIR) images. STAGE has been tested using the NIST phantom and yields intrasubject errors of only 1-2% and intrasubject variation of 2 to 5%. Contrast-to-noise ratio (CNR) measurements show that the T1WE images are comparable to the conventional T1W MP-RAGE images. Today these quantitative measures are providing new biomarkers for imaging a variety of neurodegenerative diseases (Figure 1). Results: During the last few years, we have focused on measuring iron content and neuromelanin (NM) in the substantia nigra (SN) for comparing idiopathic Parkinson’s disease (PD) with healthy controls and patients with other movement disorders. We have found that the volume of NM, the iron content of the SN, the volume of the SN and the N1 sign all together can provide an area under the curve of 95% in distinguishing PD from healthy controls.5 We have developed a template of the midbrain to allow for automatic detection and quantification of these properties. We use tSWI to enhance the N1 sign visibility. We have also used STAGE to study multiple sclerosis (MS) lesions. QSM can be used to map changes in white matter susceptibility and potentially correlated with demyelination. We provide a composite image using tSWI combined with fluid-attenuated inversion recovery (FLAIR) to highlight those lesions that are purely inflammatory from inflammatory demyelinating lesions. Recently we have begun to study the use of absolute water content as a measure of lesion atrophy. Higher water content means a higher likelihood of tissue damage. This also explains why the presence of “black holes” seen in T1W images of MS patients tends to correlate with the expanded disability status score. Conclusions: In summary, STAGE provides a comprehensive clinical imaging protocol that, combined with diffusion-weighted imaging (DWI) and FLAIR, can yield a standardized 10-minute (3T) o 15-minute (1.5T) imaging protocol of the entire brain across all manufacturers.
{"title":"Applications of strategically acquired gradient echo imaging to neurodegenerative diseases","authors":"E. Haacke","doi":"10.4081/vl.2022.10949","DOIUrl":"https://doi.org/10.4081/vl.2022.10949","url":null,"abstract":"Background: One major thrust in radiology today is image standardization with a focus on rapid, quantitative, multi-contrast data collection and processing. \u0000Methods: Strategically acquired gradient echo (STAGE) imaging1-4 is one such method that uses multiple flip angles and multiple echo times. It can provide 8 qualitative and 7 quantitative images as well as transmit field B1 transmit field and B1 receive field maps in 4-6 minutes or less on a 3T magnetic resonance (MR) scanner. STAGE provides qualitative images in the form of proton density-weighted images, T1 weighted images and T2* weighted images. STAGE provides quantitative data in the form of proton spin density (PSD), T1, T2* and susceptibility maps as well as segmentation of white matter, gray matter and cerebrospinal fluid via simulated double inversion recovery (sDIR) images. STAGE has been tested using the NIST phantom and yields intrasubject errors of only 1-2% and intrasubject variation of 2 to 5%. Contrast-to-noise ratio (CNR) measurements show that the T1WE images are comparable to the conventional T1W MP-RAGE images. Today these quantitative measures are providing new biomarkers for imaging a variety of neurodegenerative diseases (Figure 1). \u0000Results: During the last few years, we have focused on measuring iron content and neuromelanin (NM) in the substantia nigra (SN) for comparing idiopathic Parkinson’s disease (PD) with healthy controls and patients with other movement disorders. We have found that the volume of NM, the iron content of the SN, the volume of the SN and the N1 sign all together can provide an area under the curve of 95% in distinguishing PD from healthy controls.5 We have developed a template of the midbrain to allow for automatic detection and quantification of these properties. We use tSWI to enhance the N1 sign visibility. We have also used STAGE to study multiple sclerosis (MS) lesions. QSM can be used to map changes in white matter susceptibility and potentially correlated with demyelination. We provide a composite image using tSWI combined with fluid-attenuated inversion recovery (FLAIR) to highlight those lesions that are purely inflammatory from inflammatory demyelinating lesions. Recently we have begun to study the use of absolute water content as a measure of lesion atrophy. Higher water content means a higher likelihood of tissue damage. This also explains why the presence of “black holes” seen in T1W images of MS patients tends to correlate with the expanded disability status score. \u0000Conclusions: In summary, STAGE provides a comprehensive clinical imaging protocol that, combined with diffusion-weighted imaging (DWI) and FLAIR, can yield a standardized 10-minute (3T) o 15-minute (1.5T) imaging protocol of the entire brain across all manufacturers.","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"238 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121307913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chenyang Li, Marco Muccio, Li Jiang, Zhe Sun, S. Buch, Jiangyang Zhang, E. Haacke, Y. Ge
Background: The current understanding of the venous system in the hippocampus is mostly based on histological and autopsy studies.1 However, the main disadvantage is that it only reveals the anatomy of the vascular system at the post-mortem stage and lacks physiological aspects associated with neuronal metabolism. In vivo characterization of the venous system using susceptibility weighted imaging (SWI) at 7 T could provide valuable information on both venous anatomy and blood oxygen saturation, through high-resolution SWI venography2 and quantitative susceptibility mapping (QSM).3 In this study, we aim to elucidate the hierarchical network of the hippocampal venous system and then test the feasibility of using venous susceptibility to characterize venous oxygenation level changes related to neurodegeneration. Methods: Seven healthy volunteers were recruited for this study. We used high in-plane resolution of flow-compensated dual-echo gradient echo sequence (TE1/TE2/TR=7.5/15/22 ms, voxel size: 0.25*0.25*1 mm). SWI and QSM were then reconstructed using the iterative SWI and mapping (iterative SWIM) algorithm,3 as shown in Figure 1. Hippocampus masks were extracted from the T1-MPRAGE image, which was transformed to SWI space afterwards. To reduce the partial volume effect from the tissue-vessel boundary, we extract the venous susceptibility value from each voxel along the centerline of the vessels. Results: High-resolution in vivo mapping of hippocampal venous vasculature exhibits a high analogy to Duvernoy’s reference4 for hippocampal vascularization. As shown in Figure 1, there is a shape of venous arch near the fimbria of the hippocampus, and small veins extending through the arch are possibly the intrahippocampal veins. The intrahippocampal veins will eventually reach the inferior ventricular vein (IVV) (anteriorly) and medial atrial vein (MAV) (posteriorly), before joining the basal vein of Rosenthal (BVR). For venous susceptibility quantification, Figure 1 shows the representative color-coded QSM for centerline extraction on BVR. Conclusions: Our results showed improved visualization of the micro venous system in the hippocampus using high-resolution 7 T SWI data without the contrast agent.5 In summary, the characterization of venous QSM in major tributaries related to the hippocampus offers a novel perspective on oxygen utilization in the hippocampus, which may be useful for studying age-related dementia. We delineated the hierarchical network of the hippocampus venous system using SWI/QSM at 7 T and extract the venous density and venous susceptibility value in hippocampus-related small veins and major venous tributaries, as an overall measure for venous oxygenation level related to the hippocampus, which may be used as an early marker for hippocampal atrophy in Alzheimer’s disease.
{"title":"In vivo mapping of hippocampal venous vasculature and oxygen saturation using dual-echo SWI/QSM at 7 T: a potential marker for neurodegeneration","authors":"Chenyang Li, Marco Muccio, Li Jiang, Zhe Sun, S. Buch, Jiangyang Zhang, E. Haacke, Y. Ge","doi":"10.4081/vl.2022.10966","DOIUrl":"https://doi.org/10.4081/vl.2022.10966","url":null,"abstract":"Background: The current understanding of the venous system in the hippocampus is mostly based on histological and autopsy studies.1 However, the main disadvantage is that it only reveals the anatomy of the vascular system at the post-mortem stage and lacks physiological aspects associated with neuronal metabolism. In vivo characterization of the venous system using susceptibility weighted imaging (SWI) at 7 T could provide valuable information on both venous anatomy and blood oxygen saturation, through high-resolution SWI venography2 and quantitative susceptibility mapping (QSM).3 In this study, we aim to elucidate the hierarchical network of the hippocampal venous system and then test the feasibility of using venous susceptibility to characterize venous oxygenation level changes related to neurodegeneration. \u0000Methods: Seven healthy volunteers were recruited for this study. We used high in-plane resolution of flow-compensated dual-echo gradient echo sequence (TE1/TE2/TR=7.5/15/22 ms, voxel size: 0.25*0.25*1 mm). SWI and QSM were then reconstructed using the iterative SWI and mapping (iterative SWIM) algorithm,3 as shown in Figure 1. Hippocampus masks were extracted from the T1-MPRAGE image, which was transformed to SWI space afterwards. To reduce the partial volume effect from the tissue-vessel boundary, we extract the venous susceptibility value from each voxel along the centerline of the vessels. \u0000Results: High-resolution in vivo mapping of hippocampal venous vasculature exhibits a high analogy to Duvernoy’s reference4 for hippocampal vascularization. As shown in Figure 1, there is a shape of venous arch near the fimbria of the hippocampus, and small veins extending through the arch are possibly the intrahippocampal veins. The intrahippocampal veins will eventually reach the inferior ventricular vein (IVV) (anteriorly) and medial atrial vein (MAV) (posteriorly), before joining the basal vein of Rosenthal (BVR). For venous susceptibility quantification, Figure 1 shows the representative color-coded QSM for centerline extraction on BVR. \u0000Conclusions: Our results showed improved visualization of the micro venous system in the hippocampus using high-resolution 7 T SWI data without the contrast agent.5 In summary, the characterization of venous QSM in major tributaries related to the hippocampus offers a novel perspective on oxygen utilization in the hippocampus, which may be useful for studying age-related dementia. We delineated the hierarchical network of the hippocampus venous system using SWI/QSM at 7 T and extract the venous density and venous susceptibility value in hippocampus-related small veins and major venous tributaries, as an overall measure for venous oxygenation level related to the hippocampus, which may be used as an early marker for hippocampal atrophy in Alzheimer’s disease.","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124809115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. M. Laganá, A. Pirastru, Sonia Di Tella, Francesca Ferrari, L. Pelizzari, M. Cazzoli, N. Alperin, N. Jin, D. Zacà, G. Baselli, F. Baglio
Background. A link between various pathological conditions and blood and cerebrospinal fluid (CSF) flow alterations has been suggested by numerous studies.1 The blood and CSF dynamics are influenced by many factors, such as posture,2 heart beating, and thoracic pressure changes during respiration.2,3 The blood/CSF can be estimated using phase-contrast (PC) – magnetic resonance imaging (MRI). However, the clinical cardiac-gated cine PC-MRI requires several heartbeats to form the time-resolved flow images covering the entire cardiac cycle, not allowing to assess beat-by-beat variability differences and respiratory-driven flow changes. To overcome these limitations, we recently used a real-time (RT)-PC prototype for the study of blood and CSF flow rate modulations, showing low-frequency oscillations (Mayer waves).4 With the same MRI technique, in the current study we focused on assessing the cardiac and respiratory modulations on the blood and CSF flow rates, and the effects of different respiration modes. Methods. Thirty healthy volunteers (21 females, median age=26 years old, age range= 19-57 years old) were examined with a 3 T scanner. RT-PC sequences (Figure 1) allowed for a quantification of the flow rates of internal carotid arteries (ICAs), internal jugular veins (IJVs), and CSF at the first cervical level. The superior sagittal sinus (SSS) was also studied in 16 subjects.5 The flow rates were estimated with a temporal resolution of 58.5 ms for the blood, and 94 ms for the CSF. Each RT-PC lasted 60 seconds and was repeated three times: while the subject breathed with free (F) breathing, at a constant rate with a normal (PN) or forced (PD) strength. The systolic, diastolic and average flow rates and their power spectral densities were computed. High and very-high frequency peaks were identified on the spectra. Frequencies associated to the identified peaks were compared to the respiratory and cardiac frequencies estimated by a thoracic band and a pulse oximeter. The area under the spectra, normalized by the flow rate variance, was computed in the respiratory and cardiac frequency ranges (0.5 Hz-wide ranges, centered on the cardiac or breathing frequency peaks, respectively). Results. The frequencies associated with the spectral peaks were not significantly different compared to the respiratory and cardiac frequencies, for all regions and breathing modes. The average blood flow rate and the diastolic CSF peak progressively decreased from F to PN to PD breathing, the flow rate variance remained stable, and only the ICAs cross-sectional area decreased. The respiratory modulation increased with PD breathing compared with F and PN, while the cardiac modulations were less predominant for all the structures of interest. Conclusions. Using the RT-PC sequence we showed that the blood and CSF flow rates were modulated at the respiratory and cardiac frequencies. The observed reduced blood flow rate during forced breathing in the arteries and conseque
{"title":"Measuring respiratory and cardiac influences on blood and cerebrospinal fluid flow with real-time MRI","authors":"M. M. Laganá, A. Pirastru, Sonia Di Tella, Francesca Ferrari, L. Pelizzari, M. Cazzoli, N. Alperin, N. Jin, D. Zacà, G. Baselli, F. Baglio","doi":"10.4081/vl.2022.10954","DOIUrl":"https://doi.org/10.4081/vl.2022.10954","url":null,"abstract":"Background. A link between various pathological conditions and blood and cerebrospinal fluid (CSF) flow alterations has been suggested by numerous studies.1 The blood and CSF dynamics are influenced by many factors, such as posture,2 heart beating, and thoracic pressure changes during respiration.2,3 The blood/CSF can be estimated using phase-contrast (PC) – magnetic resonance imaging (MRI). However, the clinical cardiac-gated cine PC-MRI requires several heartbeats to form the time-resolved flow images covering the entire cardiac cycle, not allowing to assess beat-by-beat variability differences and respiratory-driven flow changes. To overcome these limitations, we recently used a real-time (RT)-PC prototype for the study of blood and CSF flow rate modulations, showing low-frequency oscillations (Mayer waves).4 With the same MRI technique, in the current study we focused on assessing the cardiac and respiratory modulations on the blood and CSF flow rates, and the effects of different respiration modes. \u0000Methods. Thirty healthy volunteers (21 females, median age=26 years old, age range= 19-57 years old) were examined with a 3 T scanner. RT-PC sequences (Figure 1) allowed for a quantification of the flow rates of internal carotid arteries (ICAs), internal jugular veins (IJVs), and CSF at the first cervical level. The superior sagittal sinus (SSS) was also studied in 16 subjects.5 The flow rates were estimated with a temporal resolution of 58.5 ms for the blood, and 94 ms for the CSF. Each RT-PC lasted 60 seconds and was repeated three times: while the subject breathed with free (F) breathing, at a constant rate with a normal (PN) or forced (PD) strength. The systolic, diastolic and average flow rates and their power spectral densities were computed. High and very-high frequency peaks were identified on the spectra. Frequencies associated to the identified peaks were compared to the respiratory and cardiac frequencies estimated by a thoracic band and a pulse oximeter. The area under the spectra, normalized by the flow rate variance, was computed in the respiratory and cardiac frequency ranges (0.5 Hz-wide ranges, centered on the cardiac or breathing frequency peaks, respectively). \u0000Results. The frequencies associated with the spectral peaks were not significantly different compared to the respiratory and cardiac frequencies, for all regions and breathing modes. The average blood flow rate and the diastolic CSF peak progressively decreased from F to PN to PD breathing, the flow rate variance remained stable, and only the ICAs cross-sectional area decreased. The respiratory modulation increased with PD breathing compared with F and PN, while the cardiac modulations were less predominant for all the structures of interest. \u0000 Conclusions. Using the RT-PC sequence we showed that the blood and CSF flow rates were modulated at the respiratory and cardiac frequencies. The observed reduced blood flow rate during forced breathing in the arteries and conseque","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125934480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Alzheimer’s disease pathologies and cerebrovascular disease (CVD) are two prominent pathological contributors to the cognitive decline seen with aging and in Alzheimer’s disease and Alzheimer’s related dementias (AD/ADRD). The burden of AD pathologies (amyloid and tau) is now measurable in vivo, but the multiplicity of the CVD processes and the heterogeneity in the mechanisms impedes accounting for them in cognitive aging and AD/ADRD studies. Not accounting for these CVD processes prevents us from identifying vascular contributions to cognitive impairment and dementia (VCID). Methods: In the last few years, we have conducted a series of studies to understand VCID in the population-based sample of Mayo Clinic Study of Aging (n=1500+ participants, with positron emission tomography (PET) and magnetic resonance imaging (MRI) imaging and longitudinal neuropsychological assessments). Results: We found that regional diffusion MRI markers specifically quantification of the genu (anterior) of the corpus callosum captures early systemic vascular risk-related changes.1 Using post-mortem data in a subset of participants with antemortem diffusion MRI, we found that diffusion MRI markers are more specific to the extent of CVD neuropathology seen on post-mortem tissue in comparison to visible lesions on MR.2 These early systemic vascular risk changes observed in the genu of the corpus callosum were predictive of future brain atrophy and cognitive decline.3 Given that FLAIR, T2*GRE/SWI, and diffusion MRI are the commonly acquired images in AD/ADRD studies for CVD assessment, we also evaluated which source of information among WMH, microbleeds, and infarctions would be most useful for capturing VCID. We found that a combination of white matter hyperintensities (WMH) and diffusion changes in the genu of the corpus callosum were key predictors of future cognitive decline across all cognitive domains and aided in capturing the dynamic ongoing white matter damage due to VCID.4 Further, the information provided by this combination biomarker had a similar impact on cognitive health as cortical amyloid deposition (Figure 1). These results highlight the importance of accurately accounting for VCID in AD/ADRD research and clinical studies. Conclusions: Our current work has been focused on refining the diffusion markers using advanced diffusion MRI models for capturing early changes due to VCID. We have found that advanced models may be additionally useful for distinguishing the underlying substrate of cognitive impairment in older adults.5 Specifically, VCID can be captured using anterior corpus callosum diffusion changes in comparison to neurodegenerative processes (caused by tau deposition or TDP-43 pathology) can be captured using temporal lobe diffusion changes. The knowledge gained so far coupled with newer quantification and processing methods has brought us closer to VCID biomarkers based on diffusion MRI that can be easily incorporated in AD/ADRD st
{"title":"Incorporating regional diffusion MRI-based VCID biomarkers in aging and dementia studies","authors":"P. Vemuri","doi":"10.4081/vl.2022.10959","DOIUrl":"https://doi.org/10.4081/vl.2022.10959","url":null,"abstract":"Background: Alzheimer’s disease pathologies and cerebrovascular disease (CVD) are two prominent pathological contributors to the cognitive decline seen with aging and in Alzheimer’s disease and Alzheimer’s related dementias (AD/ADRD). The burden of AD pathologies (amyloid and tau) is now measurable in vivo, but the multiplicity of the CVD processes and the heterogeneity in the mechanisms impedes accounting for them in cognitive aging and AD/ADRD studies. Not accounting for these CVD processes prevents us from identifying vascular contributions to cognitive impairment and dementia (VCID). \u0000Methods: In the last few years, we have conducted a series of studies to understand VCID in the population-based sample of Mayo Clinic Study of Aging (n=1500+ participants, with positron emission tomography (PET) and magnetic resonance imaging (MRI) imaging and longitudinal neuropsychological assessments). \u0000Results: We found that regional diffusion MRI markers specifically quantification of the genu (anterior) of the corpus callosum captures early systemic vascular risk-related changes.1 Using post-mortem data in a subset of participants with antemortem diffusion MRI, we found that diffusion MRI markers are more specific to the extent of CVD neuropathology seen on post-mortem tissue in comparison to visible lesions on MR.2 These early systemic vascular risk changes observed in the genu of the corpus callosum were predictive of future brain atrophy and cognitive decline.3 Given that FLAIR, T2*GRE/SWI, and diffusion MRI are the commonly acquired images in AD/ADRD studies for CVD assessment, we also evaluated which source of information among WMH, microbleeds, and infarctions would be most useful for capturing VCID. We found that a combination of white matter hyperintensities (WMH) and diffusion changes in the genu of the corpus callosum were key predictors of future cognitive decline across all cognitive domains and aided in capturing the dynamic ongoing white matter damage due to VCID.4 Further, the information provided by this combination biomarker had a similar impact on cognitive health as cortical amyloid deposition (Figure 1). These results highlight the importance of accurately accounting for VCID in AD/ADRD research and clinical studies. \u0000Conclusions: Our current work has been focused on refining the diffusion markers using advanced diffusion MRI models for capturing early changes due to VCID. We have found that advanced models may be additionally useful for distinguishing the underlying substrate of cognitive impairment in older adults.5 Specifically, VCID can be captured using anterior corpus callosum diffusion changes in comparison to neurodegenerative processes (caused by tau deposition or TDP-43 pathology) can be captured using temporal lobe diffusion changes. The knowledge gained so far coupled with newer quantification and processing methods has brought us closer to VCID biomarkers based on diffusion MRI that can be easily incorporated in AD/ADRD st","PeriodicalId":421508,"journal":{"name":"Veins and Lymphatics","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128395204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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