The Experts below are selected from a list of 156 Experts worldwide ranked by ideXlab platform

Anne M. Comi - One of the best experts on this subject based on the ideXlab platform.

  • Sturge-Weber Syndrome and Related Cerebrovascular Malformation Syndromes
    Oxford Medicine Online, 2017
    Co-Authors: Angela Quain, Anne M. Comi
    Abstract:

    Sturge-Weber syndrome is a rare disorder presenting with a capillary Malformation, better known as a port-wine birthmark, on the upper face, glaucoma, and a leptomeningeal angioma. Most children develop seizures and strokes, with variable degrees of neurodevelopmental impairments including hemiparesis, visual field deficits, cognitive deficits, epilepsy, and migraines. In 2013, a somatic activating mutation in GNAQ was identified in the capillary Malformations and leptomeningeal angiomas of Sturge-Weber patients. In the diagnosis of Sturge-Weber syndrome, contrast-enhanced imaging is essential to the diagnosis of brain involvement. Functional imaging has demonstrated impaired venous drainage and a role for seizures in exacerbating perfusion deficits. Aggressive seizure management is fundamental to treatment. Some data supports the use of low-dose aspirin to reduce the occurrence of strokelike episodes and seizures.

  • sturge weber syndrome and port wine stains caused by somatic mutation in gnaq
    The New England Journal of Medicine, 2013
    Co-Authors: Matthew D Shirley, Hao Tang, Carol J Gallione, Joseph D Baugher, Laurence P Frelin, Bernard L Cohen, Paula E North, Douglas A Marchuk, Anne M. Comi
    Abstract:

    The Sturge–Weber syndrome is a sporadic congenital neurocutaneous disorder characterized by a port-wine stain affecting the skin in the distribution of the ophthalmic branch of the trigeminal nerve, abnormal capillary venous vessels in the leptomeninges of the brain and choroid, glaucoma, seizures, stroke, and intellectual disability. It has been hypothesized that somatic mosaic mutations disrupting vascular development cause both the Sturge–Weber syndrome and port-wine stains, and the severity and extent of presentation are determined by the developmental time point at which the mutations occurred. To date, no such mutation has been identified. Methods We performed whole-genome sequencing of DNA from paired samples of visibly affected and normal tissue from 3 persons with the Sturge–Weber syndrome. We tested for the presence of a somatic mosaic mutation in 97 samples from 50 persons with the Sturge–Weber syndrome, a port-wine stain, or neither (controls), using amplicon sequencing and SNaPshot assays, and investigated the effects of the mutation on downstream signaling, using phosphorylation-specific antibodies for relevant effectors and a luciferase reporter assay. Results We identified a nonsynonymous single-nucleotide variant (c.548G→A, p.Arg183Gln) in GNAQ in samples of affected tissue from 88% of the participants (23 of 26) with the Sturge–Weber syndrome and from 92% of the participants (12 of 13) with apparently nonsyndromic port-wine stains, but not in any of the samples of affected tissue from 4 participants with an unrelated Cerebrovascular Malformation or in any of the samples from the 6 controls. The prevalence of the mutant allele in affected tissues ranged from 1.0 to 18.1%. Extracellular signal-regulated kinase activity was modestly increased during transgenic expression of mutant Gα q. Conclusions The Sturge–Weber syndrome and port-wine stains are caused by a somatic activating mutation in GNAQ. This finding confirms a long-standing hypothesis. (Funded by the National Institutes of Health and Hunter’s Dream for a Cure Foundation.)

Youngho Seo - One of the best experts on this subject based on the ideXlab platform.

  • Quantitative Assessment of Cerebrovascular Malformation using18F-GE180 PET/MRI
    The Journal of Nuclear Medicine, 2020
    Co-Authors: Sally Kim, Janine M. Lupo, Yicheng Chen, Helen Kim, Youngho Seo
    Abstract:

    209 Introduction: Neuroinflammation plays a key role in both the pathogenesis and the progression of cerebral cavernous Malformations (CCM) and brain arteriovenous Malformations (BAVM). [18F]GE-180 is a translocator protein (TSPO) targeting PET tracer, developed for neuroinflammation imaging. The objective of this study was to describe characteristics of [18F]GE-180 uptake in the brains of patients with CCM and to investigate whether a functional polymorphism in the TSPO p.Thr147Ala is effective for [18F]GE-180 PET screening. Methods: Six patients (five CCM and one BAVM) with an average age 50 (five males and one female), were enrolled and scanned on a GE PET/MR system. Genotyping of TSPO Ala147Thr polymorphism was performed to classify subjects as either high affinity binders (HAB) or mixed affinity binders (MAB); low affinity binders (LAB) were excluded. Subjects underwent a 60 or 90 min PET/MR scan after the administration of 8.2±1.9 mCi [18F]GE-180. For quantification of the radiotracer uptake, standardized uptake value (SUV), a validated method for this radiotracer was used. In addition, standardized uptake value ratio (SUVr) calculations were made using striatum as a reference. In order to derive SUVs consistently between all patients, all brain PET images were summed over 50-60 min when the total scan duration was 60 minutes or 60-90 min when the total scan duration was 90 minutes, and were normalized to an AAL-ROI template to derive SUVs in defined brain regions using PMOD (version 3.3). For the lesion specific SUVs, quantitative susceptibility maps (QSM), that were acquired simultaneously with the PET data, were used to define the location of the vascular Malformation. Results: Patients were classified as HAB (n=5) or MAB (n=1) based on genotype. Low [18F]GE-180 uptake was seen globally in non-lesion brain tissue ROIs, and lesion-specific uptake was visible as seen in Fig. 1. The temporal pole and cuneus showed high radiotracer uptake, the paracentral lobule and hippocampus showed moderate uptake, and striatum had the lowest uptake, with average SUVs of 0.63, 0.59, 0.55, 0.53 and 0.32, respectively. The regional SUVr was 1.95,1.82, 1.68 and 1.64, respectively. The size of lesions ranged between 3.2 mm3 and 3.8 cm3. Average CCM SUV (g/ml) and SUVr were 0.55±0.22 and 1.51±0.52, respectively. Conclusions: The distribution characteristics of [18F]GE-180 in the brain has demonstrated the potential of this tracer as a marker of neuroinflammation that may be relevant for tracking CCM disease progression and evaluating the effectiveness of potential drug therapies in future clinical trials.

  • quantitative assessment of Cerebrovascular Malformation using18f ge180 pet mri
    The Journal of Nuclear Medicine, 2020
    Co-Authors: Sally Kim, Janine M. Lupo, Yicheng Chen, Helen Kim, Youngho Seo
    Abstract:

    209 Introduction: Neuroinflammation plays a key role in both the pathogenesis and the progression of cerebral cavernous Malformations (CCM) and brain arteriovenous Malformations (BAVM). [18F]GE-180 is a translocator protein (TSPO) targeting PET tracer, developed for neuroinflammation imaging. The objective of this study was to describe characteristics of [18F]GE-180 uptake in the brains of patients with CCM and to investigate whether a functional polymorphism in the TSPO p.Thr147Ala is effective for [18F]GE-180 PET screening. Methods: Six patients (five CCM and one BAVM) with an average age 50 (five males and one female), were enrolled and scanned on a GE PET/MR system. Genotyping of TSPO Ala147Thr polymorphism was performed to classify subjects as either high affinity binders (HAB) or mixed affinity binders (MAB); low affinity binders (LAB) were excluded. Subjects underwent a 60 or 90 min PET/MR scan after the administration of 8.2±1.9 mCi [18F]GE-180. For quantification of the radiotracer uptake, standardized uptake value (SUV), a validated method for this radiotracer was used. In addition, standardized uptake value ratio (SUVr) calculations were made using striatum as a reference. In order to derive SUVs consistently between all patients, all brain PET images were summed over 50-60 min when the total scan duration was 60 minutes or 60-90 min when the total scan duration was 90 minutes, and were normalized to an AAL-ROI template to derive SUVs in defined brain regions using PMOD (version 3.3). For the lesion specific SUVs, quantitative susceptibility maps (QSM), that were acquired simultaneously with the PET data, were used to define the location of the vascular Malformation. Results: Patients were classified as HAB (n=5) or MAB (n=1) based on genotype. Low [18F]GE-180 uptake was seen globally in non-lesion brain tissue ROIs, and lesion-specific uptake was visible as seen in Fig. 1. The temporal pole and cuneus showed high radiotracer uptake, the paracentral lobule and hippocampus showed moderate uptake, and striatum had the lowest uptake, with average SUVs of 0.63, 0.59, 0.55, 0.53 and 0.32, respectively. The regional SUVr was 1.95,1.82, 1.68 and 1.64, respectively. The size of lesions ranged between 3.2 mm3 and 3.8 cm3. Average CCM SUV (g/ml) and SUVr were 0.55±0.22 and 1.51±0.52, respectively. Conclusions: The distribution characteristics of [18F]GE-180 in the brain has demonstrated the potential of this tracer as a marker of neuroinflammation that may be relevant for tracking CCM disease progression and evaluating the effectiveness of potential drug therapies in future clinical trials.

Sally Kim - One of the best experts on this subject based on the ideXlab platform.

  • Quantitative Assessment of Cerebrovascular Malformation using18F-GE180 PET/MRI
    The Journal of Nuclear Medicine, 2020
    Co-Authors: Sally Kim, Janine M. Lupo, Yicheng Chen, Helen Kim, Youngho Seo
    Abstract:

    209 Introduction: Neuroinflammation plays a key role in both the pathogenesis and the progression of cerebral cavernous Malformations (CCM) and brain arteriovenous Malformations (BAVM). [18F]GE-180 is a translocator protein (TSPO) targeting PET tracer, developed for neuroinflammation imaging. The objective of this study was to describe characteristics of [18F]GE-180 uptake in the brains of patients with CCM and to investigate whether a functional polymorphism in the TSPO p.Thr147Ala is effective for [18F]GE-180 PET screening. Methods: Six patients (five CCM and one BAVM) with an average age 50 (five males and one female), were enrolled and scanned on a GE PET/MR system. Genotyping of TSPO Ala147Thr polymorphism was performed to classify subjects as either high affinity binders (HAB) or mixed affinity binders (MAB); low affinity binders (LAB) were excluded. Subjects underwent a 60 or 90 min PET/MR scan after the administration of 8.2±1.9 mCi [18F]GE-180. For quantification of the radiotracer uptake, standardized uptake value (SUV), a validated method for this radiotracer was used. In addition, standardized uptake value ratio (SUVr) calculations were made using striatum as a reference. In order to derive SUVs consistently between all patients, all brain PET images were summed over 50-60 min when the total scan duration was 60 minutes or 60-90 min when the total scan duration was 90 minutes, and were normalized to an AAL-ROI template to derive SUVs in defined brain regions using PMOD (version 3.3). For the lesion specific SUVs, quantitative susceptibility maps (QSM), that were acquired simultaneously with the PET data, were used to define the location of the vascular Malformation. Results: Patients were classified as HAB (n=5) or MAB (n=1) based on genotype. Low [18F]GE-180 uptake was seen globally in non-lesion brain tissue ROIs, and lesion-specific uptake was visible as seen in Fig. 1. The temporal pole and cuneus showed high radiotracer uptake, the paracentral lobule and hippocampus showed moderate uptake, and striatum had the lowest uptake, with average SUVs of 0.63, 0.59, 0.55, 0.53 and 0.32, respectively. The regional SUVr was 1.95,1.82, 1.68 and 1.64, respectively. The size of lesions ranged between 3.2 mm3 and 3.8 cm3. Average CCM SUV (g/ml) and SUVr were 0.55±0.22 and 1.51±0.52, respectively. Conclusions: The distribution characteristics of [18F]GE-180 in the brain has demonstrated the potential of this tracer as a marker of neuroinflammation that may be relevant for tracking CCM disease progression and evaluating the effectiveness of potential drug therapies in future clinical trials.

  • quantitative assessment of Cerebrovascular Malformation using18f ge180 pet mri
    The Journal of Nuclear Medicine, 2020
    Co-Authors: Sally Kim, Janine M. Lupo, Yicheng Chen, Helen Kim, Youngho Seo
    Abstract:

    209 Introduction: Neuroinflammation plays a key role in both the pathogenesis and the progression of cerebral cavernous Malformations (CCM) and brain arteriovenous Malformations (BAVM). [18F]GE-180 is a translocator protein (TSPO) targeting PET tracer, developed for neuroinflammation imaging. The objective of this study was to describe characteristics of [18F]GE-180 uptake in the brains of patients with CCM and to investigate whether a functional polymorphism in the TSPO p.Thr147Ala is effective for [18F]GE-180 PET screening. Methods: Six patients (five CCM and one BAVM) with an average age 50 (five males and one female), were enrolled and scanned on a GE PET/MR system. Genotyping of TSPO Ala147Thr polymorphism was performed to classify subjects as either high affinity binders (HAB) or mixed affinity binders (MAB); low affinity binders (LAB) were excluded. Subjects underwent a 60 or 90 min PET/MR scan after the administration of 8.2±1.9 mCi [18F]GE-180. For quantification of the radiotracer uptake, standardized uptake value (SUV), a validated method for this radiotracer was used. In addition, standardized uptake value ratio (SUVr) calculations were made using striatum as a reference. In order to derive SUVs consistently between all patients, all brain PET images were summed over 50-60 min when the total scan duration was 60 minutes or 60-90 min when the total scan duration was 90 minutes, and were normalized to an AAL-ROI template to derive SUVs in defined brain regions using PMOD (version 3.3). For the lesion specific SUVs, quantitative susceptibility maps (QSM), that were acquired simultaneously with the PET data, were used to define the location of the vascular Malformation. Results: Patients were classified as HAB (n=5) or MAB (n=1) based on genotype. Low [18F]GE-180 uptake was seen globally in non-lesion brain tissue ROIs, and lesion-specific uptake was visible as seen in Fig. 1. The temporal pole and cuneus showed high radiotracer uptake, the paracentral lobule and hippocampus showed moderate uptake, and striatum had the lowest uptake, with average SUVs of 0.63, 0.59, 0.55, 0.53 and 0.32, respectively. The regional SUVr was 1.95,1.82, 1.68 and 1.64, respectively. The size of lesions ranged between 3.2 mm3 and 3.8 cm3. Average CCM SUV (g/ml) and SUVr were 0.55±0.22 and 1.51±0.52, respectively. Conclusions: The distribution characteristics of [18F]GE-180 in the brain has demonstrated the potential of this tracer as a marker of neuroinflammation that may be relevant for tracking CCM disease progression and evaluating the effectiveness of potential drug therapies in future clinical trials.

Joseph D Baugher - One of the best experts on this subject based on the ideXlab platform.

  • sturge weber syndrome and port wine stains caused by somatic mutation in gnaq
    The New England Journal of Medicine, 2013
    Co-Authors: Matthew D Shirley, Hao Tang, Carol J Gallione, Joseph D Baugher, Laurence P Frelin, Bernard L Cohen, Paula E North, Douglas A Marchuk, Anne M. Comi
    Abstract:

    The Sturge–Weber syndrome is a sporadic congenital neurocutaneous disorder characterized by a port-wine stain affecting the skin in the distribution of the ophthalmic branch of the trigeminal nerve, abnormal capillary venous vessels in the leptomeninges of the brain and choroid, glaucoma, seizures, stroke, and intellectual disability. It has been hypothesized that somatic mosaic mutations disrupting vascular development cause both the Sturge–Weber syndrome and port-wine stains, and the severity and extent of presentation are determined by the developmental time point at which the mutations occurred. To date, no such mutation has been identified. Methods We performed whole-genome sequencing of DNA from paired samples of visibly affected and normal tissue from 3 persons with the Sturge–Weber syndrome. We tested for the presence of a somatic mosaic mutation in 97 samples from 50 persons with the Sturge–Weber syndrome, a port-wine stain, or neither (controls), using amplicon sequencing and SNaPshot assays, and investigated the effects of the mutation on downstream signaling, using phosphorylation-specific antibodies for relevant effectors and a luciferase reporter assay. Results We identified a nonsynonymous single-nucleotide variant (c.548G→A, p.Arg183Gln) in GNAQ in samples of affected tissue from 88% of the participants (23 of 26) with the Sturge–Weber syndrome and from 92% of the participants (12 of 13) with apparently nonsyndromic port-wine stains, but not in any of the samples of affected tissue from 4 participants with an unrelated Cerebrovascular Malformation or in any of the samples from the 6 controls. The prevalence of the mutant allele in affected tissues ranged from 1.0 to 18.1%. Extracellular signal-regulated kinase activity was modestly increased during transgenic expression of mutant Gα q. Conclusions The Sturge–Weber syndrome and port-wine stains are caused by a somatic activating mutation in GNAQ. This finding confirms a long-standing hypothesis. (Funded by the National Institutes of Health and Hunter’s Dream for a Cure Foundation.)

Yicheng Chen - One of the best experts on this subject based on the ideXlab platform.

  • Quantitative Assessment of Cerebrovascular Malformation using18F-GE180 PET/MRI
    The Journal of Nuclear Medicine, 2020
    Co-Authors: Sally Kim, Janine M. Lupo, Yicheng Chen, Helen Kim, Youngho Seo
    Abstract:

    209 Introduction: Neuroinflammation plays a key role in both the pathogenesis and the progression of cerebral cavernous Malformations (CCM) and brain arteriovenous Malformations (BAVM). [18F]GE-180 is a translocator protein (TSPO) targeting PET tracer, developed for neuroinflammation imaging. The objective of this study was to describe characteristics of [18F]GE-180 uptake in the brains of patients with CCM and to investigate whether a functional polymorphism in the TSPO p.Thr147Ala is effective for [18F]GE-180 PET screening. Methods: Six patients (five CCM and one BAVM) with an average age 50 (five males and one female), were enrolled and scanned on a GE PET/MR system. Genotyping of TSPO Ala147Thr polymorphism was performed to classify subjects as either high affinity binders (HAB) or mixed affinity binders (MAB); low affinity binders (LAB) were excluded. Subjects underwent a 60 or 90 min PET/MR scan after the administration of 8.2±1.9 mCi [18F]GE-180. For quantification of the radiotracer uptake, standardized uptake value (SUV), a validated method for this radiotracer was used. In addition, standardized uptake value ratio (SUVr) calculations were made using striatum as a reference. In order to derive SUVs consistently between all patients, all brain PET images were summed over 50-60 min when the total scan duration was 60 minutes or 60-90 min when the total scan duration was 90 minutes, and were normalized to an AAL-ROI template to derive SUVs in defined brain regions using PMOD (version 3.3). For the lesion specific SUVs, quantitative susceptibility maps (QSM), that were acquired simultaneously with the PET data, were used to define the location of the vascular Malformation. Results: Patients were classified as HAB (n=5) or MAB (n=1) based on genotype. Low [18F]GE-180 uptake was seen globally in non-lesion brain tissue ROIs, and lesion-specific uptake was visible as seen in Fig. 1. The temporal pole and cuneus showed high radiotracer uptake, the paracentral lobule and hippocampus showed moderate uptake, and striatum had the lowest uptake, with average SUVs of 0.63, 0.59, 0.55, 0.53 and 0.32, respectively. The regional SUVr was 1.95,1.82, 1.68 and 1.64, respectively. The size of lesions ranged between 3.2 mm3 and 3.8 cm3. Average CCM SUV (g/ml) and SUVr were 0.55±0.22 and 1.51±0.52, respectively. Conclusions: The distribution characteristics of [18F]GE-180 in the brain has demonstrated the potential of this tracer as a marker of neuroinflammation that may be relevant for tracking CCM disease progression and evaluating the effectiveness of potential drug therapies in future clinical trials.

  • quantitative assessment of Cerebrovascular Malformation using18f ge180 pet mri
    The Journal of Nuclear Medicine, 2020
    Co-Authors: Sally Kim, Janine M. Lupo, Yicheng Chen, Helen Kim, Youngho Seo
    Abstract:

    209 Introduction: Neuroinflammation plays a key role in both the pathogenesis and the progression of cerebral cavernous Malformations (CCM) and brain arteriovenous Malformations (BAVM). [18F]GE-180 is a translocator protein (TSPO) targeting PET tracer, developed for neuroinflammation imaging. The objective of this study was to describe characteristics of [18F]GE-180 uptake in the brains of patients with CCM and to investigate whether a functional polymorphism in the TSPO p.Thr147Ala is effective for [18F]GE-180 PET screening. Methods: Six patients (five CCM and one BAVM) with an average age 50 (five males and one female), were enrolled and scanned on a GE PET/MR system. Genotyping of TSPO Ala147Thr polymorphism was performed to classify subjects as either high affinity binders (HAB) or mixed affinity binders (MAB); low affinity binders (LAB) were excluded. Subjects underwent a 60 or 90 min PET/MR scan after the administration of 8.2±1.9 mCi [18F]GE-180. For quantification of the radiotracer uptake, standardized uptake value (SUV), a validated method for this radiotracer was used. In addition, standardized uptake value ratio (SUVr) calculations were made using striatum as a reference. In order to derive SUVs consistently between all patients, all brain PET images were summed over 50-60 min when the total scan duration was 60 minutes or 60-90 min when the total scan duration was 90 minutes, and were normalized to an AAL-ROI template to derive SUVs in defined brain regions using PMOD (version 3.3). For the lesion specific SUVs, quantitative susceptibility maps (QSM), that were acquired simultaneously with the PET data, were used to define the location of the vascular Malformation. Results: Patients were classified as HAB (n=5) or MAB (n=1) based on genotype. Low [18F]GE-180 uptake was seen globally in non-lesion brain tissue ROIs, and lesion-specific uptake was visible as seen in Fig. 1. The temporal pole and cuneus showed high radiotracer uptake, the paracentral lobule and hippocampus showed moderate uptake, and striatum had the lowest uptake, with average SUVs of 0.63, 0.59, 0.55, 0.53 and 0.32, respectively. The regional SUVr was 1.95,1.82, 1.68 and 1.64, respectively. The size of lesions ranged between 3.2 mm3 and 3.8 cm3. Average CCM SUV (g/ml) and SUVr were 0.55±0.22 and 1.51±0.52, respectively. Conclusions: The distribution characteristics of [18F]GE-180 in the brain has demonstrated the potential of this tracer as a marker of neuroinflammation that may be relevant for tracking CCM disease progression and evaluating the effectiveness of potential drug therapies in future clinical trials.