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Article: Effect of the identification group size and image resolution on the diagnostic performance of metabolic Alzheimer's disease-related pattern.

Štokelj, Eva / Tomše, Petra / Tomanič, Tadej / Dhawan, Vijay / Eidelberg, David / Trošt, Maja / Simončič, Urban

2023 Volume 13, Issue 1, Page(s) 47

Abstract: Background: Alzheimer's disease-related pattern (ADRP) is a metabolic brain biomarker of Alzheimer's disease (AD). While ADRP is being introduced into research, the effect of the size of the identification cohort and the effect of the resolution of ... ...

Abstract	Background: Alzheimer's disease-related pattern (ADRP) is a metabolic brain biomarker of Alzheimer's disease (AD). While ADRP is being introduced into research, the effect of the size of the identification cohort and the effect of the resolution of identification and validation images on ADRP's performance need to be clarified. Methods: 240 2-[ Results: ADRP's performance for the differentiation between AD patients and CN demonstrated only a marginal average AUC increase, when the number of subjects in the identification group increases (AUC increase for about 0.03 from 20 AD/20 CN to 80 AD/80 CN). However, the average of the lowest five AUC values increased with the increasing number of participants (AUC increase for about 0.07 from 20 AD/20 CN to 30 AD/30 CN and for an additional 0.02 from 30 AD/30 CN to 40 AD/40 CN). The resolution of the identification images affects ADRP's diagnostic performance only marginally in the range from 8 to 15 mm. ADRP's performance stayed optimal even when applied to validation images of resolution differing from the identification images. Conclusions: While small (20 AD/20 CN images) identification cohorts may be adequate in a favorable selection of cases, larger cohorts (at least 30 AD/30 CN images) shall be preferred to overcome possible/random biological differences and improve ADRP's diagnostic performance. ADRP's performance stays stable even when applied to the validation images with a resolution different than the resolution of the identification ones.
Language	English
Publishing date	2023-05-24
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2619892-7
ISSN	2191-219X
ISSN	2191-219X
DOI	10.1186/s13550-023-01001-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Neuroimaging evaluation of deep brain stimulation in the treatment of representative neurodegenerative and neuropsychiatric disorders.

Peng, Shichun / Dhawan, Vijay / Eidelberg, David / Ma, Yilong

Bioelectronic medicine

2021 Volume 7, Issue 1, Page(s) 4

Abstract: Brain stimulation technology has become a viable modality of reversible interventions in the effective treatment of many neurological and psychiatric disorders. It is aimed to restore brain dysfunction by the targeted delivery of specific electronic ... ...

Abstract	Brain stimulation technology has become a viable modality of reversible interventions in the effective treatment of many neurological and psychiatric disorders. It is aimed to restore brain dysfunction by the targeted delivery of specific electronic signal within or outside the brain to modulate neural activity on local and circuit levels. Development of therapeutic approaches with brain stimulation goes in tandem with the use of neuroimaging methodology in every step of the way. Indeed, multimodality neuroimaging tools have played important roles in target identification, neurosurgical planning, placement of stimulators and post-operative confirmation. They have also been indispensable in pre-treatment screen to identify potential responders and in post-treatment to assess the modulation of brain circuitry in relation to clinical outcome measures. Studies in patients to date have elucidated novel neurobiological mechanisms underlying the neuropathogenesis, action of stimulations, brain responses and therapeutic efficacy. In this article, we review some applications of deep brain stimulation for the treatment of several diseases in the field of neurology and psychiatry. We highlight how the synergistic combination of brain stimulation and neuroimaging technology is posed to accelerate the development of symptomatic therapies and bring revolutionary advances in the domain of bioelectronic medicine.
Language	English
Publishing date	2021-03-30
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2929561-0
ISSN	2332-8886 ; 2332-8886
ISSN (online)	2332-8886
ISSN	2332-8886
DOI	10.1186/s42234-021-00065-9
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Article: Stimulation of the Subthalamic Nucleus Changes Cortical-Subcortical Blood Flow Patterns During Speech: A Positron Emission Tomography Study.

Sidtis, John J / Sidtis, Diana Van Lancker / Dhawan, Vijay / Tagliati, Michele / Eidelberg, David

Frontiers in neurology

2021 Volume 12, Page(s) 684596

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2021-05-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2021.684596
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Article ; Online: Stereotyped Relationship Between Motor and Cognitive Metabolic Networks in Parkinson's Disease.

Rus, Tomaž / Schindlbeck, Katharina A / Tang, Chris C / Vo, An / Dhawan, Vijay / Trošt, Maja / Eidelberg, David

Movement disorders : official journal of the Movement Disorder Society

2022 Volume 37, Issue 11, Page(s) 2247–2256

Abstract: Background: Idiopathic Parkinson's disease (iPD) is associated with two distinct brain networks, PD-related pattern (PDRP) and PD-related cognitive pattern (PDCP), which correlate respectively with motor and cognitive symptoms. The relationship between ... ...

Abstract	Background: Idiopathic Parkinson's disease (iPD) is associated with two distinct brain networks, PD-related pattern (PDRP) and PD-related cognitive pattern (PDCP), which correlate respectively with motor and cognitive symptoms. The relationship between the two networks in individual patients is unclear. Objective: To determine whether a consistent relationship exists between these networks, we measured the difference between PDRP and PDCP expression, termed delta, on an individual basis in independent populations of patients with iPD (n = 356), patients with idiopathic REM sleep behavioral disorder (iRBD) (n = 21), patients with genotypic PD (gPD) carrying GBA1 variants (n = 12) or the LRRK2-G2019S mutation (n = 14), patients with atypical parkinsonian syndromes (n = 238), and healthy control subjects (n = 95) from the United States, Slovenia, India, and South Korea. Methods: We used [ Results: Delta was abnormally elevated in each of the four iPD samples (P < 0.05), as well as in the at-risk iRBD group (P < 0.05), with increasing values over time (P < 0.001). PDRP predominance was also present in gPD, with higher values in patients with GBA1 variants compared with the less aggressive LRRK2-G2019S mutation (P = 0.005). This trend was not observed in patients with atypical parkinsonian syndromes, who were accurately discriminated from iPD based on PDRP expression and delta (area under the curve = 0.85; P < 0.0001). Conclusions: PDRP predominance, quantified by delta, assays the spread of dysfunction from motor to cognitive networks in patients with PD. Delta may therefore aid in differential diagnosis and in tracking disease progression in individual patients. © 2022 International Parkinson and Movement Disorder Society.
MeSH term(s)	Humans ; Parkinson Disease/complications ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Fluorodeoxyglucose F18/metabolism ; Positron-Emission Tomography/methods ; REM Sleep Behavior Disorder/complications ; Brain/diagnostic imaging ; Brain/metabolism ; Metabolic Networks and Pathways ; Cognition
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2022-08-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.29188
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Article ; Online: Dynamic

Peng, Shichun / Tang, Chris / Schindlbeck, Katharina / Rydzinski, Yaacov / Dhawan, Vijay / Spetsieris, Phoebe G / Ma, Yilong / Eidelberg, David

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2021

Abstract: Previous multi-center imaging studies ... ...

Abstract	Previous multi-center imaging studies with
Language	English
Publishing date	2021-03-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.120.257345
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Zs.MO 328: Show issues

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Article ; Online: Blood-brain barrier permeability in Parkinson's disease patients with and without dyskinesia.

Fujita, Koji / Peng, Shichun / Ma, Yilong / Tang, Chris C / Hellman, Matthew / Feigin, Andrew / Eidelberg, David / Dhawan, Vijay

Journal of neurology

2021 Volume 268, Issue 6, Page(s) 2246–2255

Abstract: Objective: Recent studies on a rodent model of Parkinson's disease (PD) have raised the possibility of increased blood-brain barrier (BBB) permeability, demonstrated by histology, autoradiography, and positron emission tomography (PET). However, in ... ...

Abstract	Objective: Recent studies on a rodent model of Parkinson's disease (PD) have raised the possibility of increased blood-brain barrier (BBB) permeability, demonstrated by histology, autoradiography, and positron emission tomography (PET). However, in human PD patients, in vivo evidence of increased BBB permeability is lacking. We examined the hypothesis that levodopa treatment increases BBB permeability in human subjects with PD, particularly in those with levodopa-induced dyskinesia (LID). Methods: We used rubidium-82 ( Results: Rubidium influx into brain tissue was undetectable in PD patients with or without LID, scanned on and off drug. No significant differences in regional V Conclusion: 82
MeSH term(s)	Antiparkinson Agents ; Blood-Brain Barrier/diagnostic imaging ; Dyskinesias ; Humans ; Levodopa ; Parkinson Disease/complications ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/drug therapy ; Permeability
Chemical Substances	Antiparkinson Agents ; Levodopa (46627O600J)
Language	English
Publishing date	2021-01-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-021-10411-1
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Article ; Online: Adaptive and pathological connectivity responses in Parkinson's disease brain networks.

Vo, An / Schindlbeck, Katharina A / Nguyen, Nha / Rommal, Andrea / Spetsieris, Phoebe G / Tang, Chris C / Choi, Yoon Young / Niethammer, Martin / Dhawan, Vijay / Eidelberg, David

Cerebral cortex (New York, N.Y. : 1991)

2022 Volume 33, Issue 4, Page(s) 917–932

Abstract: Functional imaging has been used extensively to identify and validate disease-specific networks as biomarkers in neurodegenerative disorders. It is not known, however, whether the connectivity patterns in these networks differ with disease progression ... ...

Abstract	Functional imaging has been used extensively to identify and validate disease-specific networks as biomarkers in neurodegenerative disorders. It is not known, however, whether the connectivity patterns in these networks differ with disease progression compared to the beneficial adaptations that may also occur over time. To distinguish the 2 responses, we focused on assortativity, the tendency for network connections to link nodes with similar properties. High assortativity is associated with unstable, inefficient flow through the network. Low assortativity, by contrast, involves more diverse connections that are also more robust and efficient. We found that in Parkinson's disease (PD), network assortativity increased over time. Assoratitivty was high in clinically aggressive genetic variants but was low for genes associated with slow progression. Dopaminergic treatment increased assortativity despite improving motor symptoms, but subthalamic gene therapy, which remodels PD networks, reduced this measure compared to sham surgery. Stereotyped changes in connectivity patterns underlie disease progression and treatment responses in PD networks.
MeSH term(s)	Humans ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/therapy ; Magnetic Resonance Imaging/methods ; Brain ; Dopamine ; Disease Progression
Chemical Substances	Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2022-03-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhac110
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Article: Prospective F-18 FDOPA PET Imaging Study in Human PD.

Dhawan, Vijay / Niethammer, Martin H / Lesser, Martin L / Pappas, Karalyn N / Hellman, Matthew / Fitzpatrick, Toni M / Bjelke, David / Singh, Jaskirat / Quatarolo, Loreta M / Choi, Yoon Young / Oh, Alice / Eidelberg, David / Chaly, Thomas

Nuclear medicine and molecular imaging

2022 Volume 56, Issue 3, Page(s) 147–157

Abstract: Purpose: We present the findings of our final prospective study submitted to the U.S. Food and Drug Administration (FDA) for New Drug Application (NDA) approval for the use of 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (F-18 FDOPA) positron emission ... ...

Abstract	Purpose: We present the findings of our final prospective study submitted to the U.S. Food and Drug Administration (FDA) for New Drug Application (NDA) approval for the use of 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (F-18 FDOPA) positron emission tomography (PET) imaging for Parkinson's disease (PD). The primary aim was to determine the sensitivity, specificity, and predictive values of F-18 FDOPA PET in parkinsonian patients with respect to clinical standard-of-truth (SOT). Secondary outcomes included the inter-rater reliability, and correlation of quantitative measures for PET with dopaminergic status. Methods: In 68 parkinsonian subjects, F-18 FDOPA PET scan from 80 to 100 min was acquired following a CT scan. Scan images were presented to one expert in F-18 FDOPA image interpretation and two physicians with prior experience in I-123 FPCIT single-photon emission computed tomography image interpretation. Fifty-six subjects completed the study with a follow-up for SOT determination. Image readers were blind to the clinical/quantitative data; SOT clinician was blind to the image data. Results: For 47 of the 56 patients, SOT was in agreement with the PET scan results. For nine patients, SOT suggested dopaminergic deficit, whereas the imaging showed normal uptake. The specificity and positive predictive values are 91% and 92%, respectively, suggesting high probability that those who test positive by the PET scan truly have dopaminergic degeneration. The sensitivity was 73%. Inter-rater agreement was 0.6-0.8 between the different readers. Conclusion: Our prospective study demonstrates high specificity and moderate sensitivity of F-18 FDOPA PET for PD. We received NDA approval in October 2019. Supplementary information: The online version contains supplementary material available at 10.1007/s13139-022-00748-4.
Language	English
Publishing date	2022-04-12
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2541855-5
ISSN	1869-3482 ; 1869-3474
ISSN (online)	1869-3482
ISSN	1869-3474
DOI	10.1007/s13139-022-00748-4
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Article ; Online: Switching Language Modes: Complementary Brain Patterns for Formulaic and Propositional Language.

Sidtis, John J / Van Lancker Sidtis, Diana / Dhawan, Vijay / Eidelberg, David

Brain connectivity

2018 Volume 8, Issue 3, Page(s) 189–196

Abstract: Language has been modeled as a rule governed behavior for generating an unlimited number of novel utterances using phonological, syntactic, and lexical processes. This view of language as essentially propositional is expanding as a contributory role of ... ...

Abstract	Language has been modeled as a rule governed behavior for generating an unlimited number of novel utterances using phonological, syntactic, and lexical processes. This view of language as essentially propositional is expanding as a contributory role of formulaic expressions (e.g., you know, have a nice day, how are you?) is increasingly recognized. The basic features of the functional anatomy of this language system have been described by studies of brain damage: left lateralization for propositional language and greater right lateralization and basal ganglia involvement for formulaic expressions. Positron emission tomography (PET) studies of cerebral blood flow (CBF) have established a cortical-subcortical pattern of brain activity predictive of syllable rate during phonological/lexical repetition. The same analytic approach was applied to analyzing brain images obtained during spontaneous monologues. Sixteen normal, right-handed, native English speakers underwent PET scanning during several language tasks. Speech rate for the repetition of phonological/lexical items was predicted by increased CBF in the left inferior frontal region and decreased CBF in the head of the right caudate nucleus, replicating previous results. A complementary cortical-subcortical pattern (CBF increased in the right inferior frontal region and decreased in the left caudate) was predictive of the use of speech formulas during monologue speech. The use of propositional language during the monologues was associated with strong left lateralization (increased CBF at the left inferior frontal region and decreased CBF at the right inferior frontal region). Normal communication involves the integration of two language modes, formulaic and novel, that have different neural substrates.
MeSH term(s)	Adult ; Aged ; Caudate Nucleus/diagnostic imaging ; Caudate Nucleus/physiology ; Cerebrovascular Circulation/physiology ; Female ; Functional Laterality/physiology ; Functional Neuroimaging/methods ; Humans ; Language ; Male ; Middle Aged ; Positron-Emission Tomography/methods ; Prefrontal Cortex/diagnostic imaging ; Prefrontal Cortex/physiology ; Speech/physiology
Language	English
Publishing date	2018-03-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2609017-X
ISSN	2158-0022 ; 2158-0014
ISSN (online)	2158-0022
ISSN	2158-0014
DOI	10.1089/brain.2017.0573
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Article ; Online: Mom and me: brain metabolism links Alzheimer disease to maternal genes.

Dhawan, Vijay / Eidelberg, David

Neurology

2009 Volume 72, Issue 6, Page(s) 486–487

MeSH term(s)	Alzheimer Disease/congenital ; Alzheimer Disease/metabolism ; Brain/metabolism ; Female ; Genetic Predisposition to Disease/genetics ; Glucose/metabolism ; Heterozygote ; Humans ; Male ; Mothers
Chemical Substances	Glucose (IY9XDZ35W2)
Language	English
Publishing date	2009-02-10
Publishing country	United States
Document type	Comment ; Editorial ; Introductory Journal Article
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/01.wnl.0000341939.31303.32
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