Initial Cerebral HM-PAO Distribution Compared to LCBF: Use of a Model Which Considers Cerebral HM-PAO Trapping Kinetics

The cerebral uptake of [99mTc]– d,l-hexamethylpropyleneamine oxime complex (HM-PAO) was compared to LCBF determined simultaneously with [14C]iodoantipyrine (IAP) using double radionuclide quantitative digital autoradiography. Awake male rats were given intravenous injections of a mixture of 50 μCi IAP and 15 mCi of HM-PAO and killed 20 s after tracer activity had first reached the brain. Two separate autoradiograms were produced from each 20 μm brain section. The autoradiograms were digitized, corrected for cross-contamination, and then converted into images of individual tracer concentration. The diffusible tracer model was used to convert the IAP concentration images into LCBF images. Regional HM-PAO concentration was found not to be linearly related to LCBF as determined with the IAP, and therefore a simple microsphere type model was inadequate in relating HM-PAO uptake to LCBF. A better HM-PAO uptake–LCBF correlation was obtained when the HM-PAO arterial input function was corrected for very rapidly produced, non-cerebrally extracted, metabolites and a kinetic model was used that considered the rate of intracerebral metabolism of HM-PAO to a retained metabolite. Even using this model, however, some differences between HM-PAO uptake and LCBF occurred in certain brain regions. Because these differences were small and the HM-PAO uptake pattern has been shown to be constant for many minutes, HM-PAO can probably be used to estimate LCBF in patients with single positron emission computed tomography (SPECT) imaging.

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Reference Region Modeling Approaches for Amphetamine Challenge Studies with [11C]FLB 457 and PET

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.237 ◽

2015 ◽

Vol 35 (4) ◽

pp. 623-629 ◽

Cited By ~ 21

Author(s):

Christine M Sandiego ◽

Jean-Dominique Gallezot ◽

Keunpoong Lim ◽

Jim Ropchan ◽

Shu-fei Lin ◽

...

Keyword(s):

Arterial Input Function ◽

Input Function ◽

Brain Regions ◽

Reference Region ◽

Reference Tissue ◽

Modeling Approaches ◽

Positron Emission ◽

Dopaminergic Dysfunction ◽

Induced Changes ◽

Tissue Models

Detecting fluctuations in synaptic dopamine levels in extrastriatal brain regions with [11C]FLB 457 and positron emission tomography (PET) is a valuable tool for studying dopaminergic dysfunction in psychiatric disorders. The evaluation of reference region modeling approaches would eliminate the need to obtain arterial input function data. Our goal was to explore the use of reference region models to estimate amphetamine-induced changes in [11C]FLB 457 dopamine D2/D3 binding. Six healthy tobacco smokers were imaged with [11C]FLB 457 at baseline and at 3 hours after amphetamine (0.4 to 0.5 mg/kg, per os) administration. Simplified reference tissue models, SRTM and SRTM2, were evaluated against the 2-tissue compartmental model (2TC) to estimate [11C]FLB 457 binding in extrastriatal regions of interest (ROIs), using the cerebellum as a reference region. No changes in distribution volume were observed in the cerebellum between scan conditions. SRTM and SRTM2 underestimated binding, compared with 2TC, in ROIs by 26% and 9%, respectively, with consistent bias between the baseline and postamphetamine scans. Postamphetamine, [11C]FLB 457 binding significantly decreased across several brain regions as measured with SRTM and SRTM2; no significant change was detected with 2TC. These data support the sensitivity of [11C]FLB 457 for measuring amphetamine-induced dopamine release in extrastriatal regions with SRTM and SRTM2.

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Robust arterial input function surrogate measurement from the superior sagittal sinus complex signal for fast dynamic contrast‐enhanced MRI in the brain

Magnetic Resonance in Medicine ◽

10.1002/mrm.28922 ◽

2021 ◽

Author(s):

Benoît Bourassa‐Moreau ◽

Réjean Lebel ◽

Guillaume Gilbert ◽

David Mathieu ◽

Martin Lepage

Keyword(s):

Arterial Input Function ◽

Superior Sagittal Sinus ◽

Input Function ◽

Complex Signal ◽

Sagittal Sinus ◽

Contrast Enhanced ◽

Surrogate Measurement ◽

The Brain ◽

Fast Dynamic ◽

Contrast Enhanced Mri

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Pain Detection and the Privacy of Subjective Experience

American Journal of Law & Medicine ◽

10.1177/009885880703300212 ◽

2007 ◽

Vol 33 (2-3) ◽

pp. 433-456 ◽

Cited By ~ 22

Author(s):

Adam J. Kolber

Keyword(s):

Subjective Experience ◽

Brain Regions ◽

Physical Pain ◽

Medical Evidence ◽

Functional Magnetic Resonance ◽

Positron Emission ◽

Pain Symptoms ◽

The Brain ◽

Insight Into ◽

Neuroimaging Techniques

A neurologist with abdominal pain goes to see a gastroenterologist for treatment. The gastroenterologist asks the neurologist where it hurts. The neurologist replies, “In my head, of course.” Indeed, while we can feel pain throughout much of our bodies, pain signals undergo most of their processing in the brain. Using neuroimaging techniques like functional magnetic resonance imaging (“fMRI”) and positron emission tomography (“PET”), researchers have more precisely identified brain regions that enable us to experience physical pain. Certain regions of the brain's cortex, for example, increase in activation when subjects are exposed to painful stimuli. Furthermore, the amount of activation increases with the intensity of the painful stimulus. These findings suggest that we may be able to gain insight into the amount of pain a particular person is experiencing by non-invasively imaging his brain.Such insight could be particularly valuable in the courtroom where we often have no definitive medical evidence to prove or disprove claims about the existence and extent of pain symptoms.

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Synthesis and preclinical evaluation of [11C]MTP38 as a novel PET ligand for phosphodiesterase 7 in the brain

10.1101/2020.10.29.354696 ◽

2020 ◽

Author(s):

Naoyuki Obokata ◽

Chie Seki ◽

Takeshi Hirata ◽

Jun Maeda ◽

Hideki Ishii ◽

...

Keyword(s):

Arterial Input Function ◽

Inflammatory Diseases ◽

Input Function ◽

Binding Potential ◽

Dependent Manner ◽

Reference Tissue ◽

Molar Activity ◽

The Brain

AbstractPurposePhosphodiesterase (PDE) 7 is a potential therapeutic target for neurological and inflammatory diseases, although in-vivo visualization of PDE7 has not been successful. In this study, we aimed to develop [11C]MTP38 as a novel positron emission tomography (PET) ligand for PDE7.Methods[11C]MTP38 was radiosynthesized by 11C-cyanation of a bromo precursor with [11C]HCN. PET scans of rat and rhesus monkey brains and in-vitro autoradiography of brain sections derived from these species were conducted with [11C]MTP38. In monkeys, dynamic PET data were analyzed with an arterial input function to calculate the total distribution volume (VT). The non-displaceable binding potential (BPND) in the striatum was also determined by a reference tissue model with cerebellar reference. Finally, striatal occupancy of PDE7 by an inhibitor was calculated in monkeys according to changes in BPND.Results[11C]MTP38 was synthesized with radiochemical purity ≥ 99.4% and molar activity of 38.6 ± 12.6 GBq/μmol. Autoradiography revealed high radioactivity in the striatum and its reduction by non-radiolabeled ligands, in contrast with unaltered autoradiographic signals in other regions. In-vivo PET after radioligand injection to rats and monkeys demonstrated that radioactivity was rapidly distributed to the brain and intensely accumulated in the striatum relative to the cerebellum. Correspondingly, estimated VT values in the monkey striatum and cerebellum were 3.59 and 2.69 mL/cm3, respectively. The cerebellar VT value was unchanged by pretreatment with unlabeled MTP38. Striatal BPND was reduced in a dose-dependent manner after pretreatment with MTP-X, a PDE7 inhibitor. Relationships between PDE7 occupancy by MTP-X and plasma MTP-X concentration could be described by Hill’s sigmoidal function.ConclusionWe have provided the first successful preclinical demonstration of in-vivo PDE7 imaging with a specific PET radioligand. [11C]MTP38 is a feasible radioligand for evaluating PDE7 in the brain and is currently being applied to a first-in-human PET study.

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Effects of early neonatal proinflammatory stress on the expression of BDNF transcripts in the brain regions of prepubertal male rats

Vavilov Journal of Genetics and Breeding ◽

10.18699/vj16.149 ◽

2016 ◽

Vol 20 (2) ◽

pp. 191-197

Author(s):

D. I. Peregud ◽

S. V. Freiman ◽

A. O. Tishkina ◽

L. S. Sokhranyaeva ◽

N. A. Lazareva ◽

...

Keyword(s):

Brain Regions ◽

Male Rats ◽

The Brain

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29 POSITRON EMISSION TOMOGRAPHY IMAGING OF BRAIN METABOLISM AND DOPAMINERGIC NEURON DESTRUCTION IN PARKINSON'S DISEASE MODEL PIG

Reproduction Fertility and Development ◽

10.1071/rdv29n1ab29 ◽

2017 ◽

Vol 29 (1) ◽

pp. 122

Author(s):

H. J. Oh ◽

J. Moon ◽

G. A. Kim ◽

S. Lee ◽

S. H. Paek ◽

...

Keyword(s):

Positron Emission Tomography ◽

Dopaminergic Neuron ◽

Brain Metabolism ◽

Brain Research ◽

Brain Regions ◽

Emission Tomography ◽

Positron Emission ◽

Significant Difference ◽

And Control ◽

The Brain

Due to similarities between human and porcine, pigs have been proposed as an excellent experimental animal for human medical research. Especially in paediatric brain research, piglets share similarities with human infants in the extent of peak brain growth at the time of birth and the growth pattern of brain. Thus, these findings have supported the wider use of pigs rather than rodents in neuroscience research. Previously, we reported the production of porcine model of Parkinson's disease (PD) by nuclear transfer using donor cell that had been stably infected with lentivirus containing the human α-synuclein gene. The purpose of this study was to determine the alternation of brain metabolism and dopaminergic neuron destruction using noninvasive method in a 2-yr-old PD model and a control pig. The positron emission tomography (PET) scan was done using Biograph TruePoint40 with a TrueV (Siemens, Munich, Germany). The [18F]N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) was administrated via the ear vein. Static images of the brain for 15 min were acquired from 2 h after injection. The 18F-fluorodeoxy-D-glucose PET (18F-FDG PET) images of the brain were obtained for 15 min at 45 min post-injection. Computed tomography (CT) scan and magnetic resonance imaging (MRI) were performed at the same location of the brain. In both MRI and CT images, there was no difference in brain regions between PD model and control pigs. However, administration of [18F]FP-CIT was markedly decreased in the bilateral putamen of the PD model pig compared with the control pigs. Moreover, [18F]FP-CIT administration was asymmetrical in the PD model pig but it was symmetrical in control pigs. Regional brain metabolism was also assessed and there was no significant difference in cortical metabolism of PD model and control pigs. We demonstrated that PET imaging could provide a foundation for translational Parkinson neuroimaging in transgenic pigs. In the present study, a 2-yr-old PD model pig showed dopaminergic neuron destruction in brain regions. Therefore, PD model pig expressing human α-synuclein gene would be an efficient model for human PD patients. This study was supported by Korea IPET (#311011–05–5-SB010), Research Institute for Veterinary Science, TS Corporation and the BK21 plus program.

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Effects of early neonatal proinflammatory stress on the expression of BDNF transcripts in the brain regions of prepubertal male rats

Russian Journal of Genetics Applied Research ◽

10.1134/s2079059717010117 ◽

2017 ◽

Vol 7 (1) ◽

pp. 121-127 ◽

Cited By ~ 1

Author(s):

D. I. Peregud ◽

S. V. Freiman ◽

A. O. Tishkina ◽

L. S. Sokhranyaeva ◽

N. A. Lazareva ◽

...

Keyword(s):

Brain Regions ◽

Male Rats ◽

The Brain

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Evaluation of Simplified Kinetic Analyses for Measurement of Brain Acetylcholinesterase Activity Using N-[11C]Methylpiperidin-4-yl Propionate and Positron Emission Tomography

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/01.wcb.0000117689.98763.6a ◽

2004 ◽

Vol 24 (6) ◽

pp. 600-611 ◽

Cited By ~ 10

Author(s):

Koichi Sato ◽

Kiyoshi Fukushi ◽

Hitoshi Shinotoh ◽

Shinichiro Nagatsuka ◽

Noriko Tanaka ◽

...

Keyword(s):

Ache Activity ◽

Arterial Input Function ◽

Acetylcholinesterase Activity ◽

Input Function ◽

Previous Method ◽

Target Tissue ◽

Standard Analysis ◽

Reference Tissue ◽

Arterial Blood ◽

Positron Emission

The applicability of two reference tissue-based analyses without arterial blood sampling for the measurement of brain regional acetylcholinesterase (AChE) activity using N-[11C]methylpiperidin-4-yl propionate ([11C]MP4P) was evaluated in 12 healthy subjects. One was a linear least squares analysis derived from Blomqvist's equation, and the other was the analysis of the ratio of target-tissue radioactivity relative to reference-tissue radioactivity proposed by Herholz and coworkers. The standard compartment analysis using arterial input function provided reliable quantification of k3 (an index of AChE activity) estimates in regions with low (neocortex and hippocampus), moderate (thalamus), and high (cerebellum) AChE activity with a coefficient of variation (COV) of 12% to 19%. However, the precise k3 value in the striatum, where AChE activity is the highest, was not obtained. The striatum was used as a reference because its time-radioactivity curve was proportional to the time integral of the arterial input function. Reliable k3 estimates were also obtained in regions with low-to-moderate AChE activity with a COV of less than 21% by striatal reference analyses, though not obtained in the cerebellum. Shape analysis, the previous method of direct k3 estimation from the shape of time-radioactivity data, gave k3 estimates in the cortex and thalamus with a somewhat larger COV. In comparison with the standard analysis, a moderate overestimation of k3 by 9% to 18% in the linear analysis and a moderate underestimation by 2% to 13% in the Herholz method were observed, which were appropriately explained by the results of computer simulation. In conclusion, simplified kinetic analyses are practical and useful for the routine analysis of clinical [11C]MP4P studies and are nearly as effective as the standard analysis for detecting regions with abnormal AChE activity.

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Neuroimaging in dementia and depression

Advances in Psychiatric Treatment ◽

10.1192/apt.6.2.109 ◽

2000 ◽

Vol 6 (2) ◽

pp. 109-119 ◽

Cited By ~ 7

Author(s):

John O'Brien ◽

Bob Barber

Keyword(s):

Computed Tomography ◽

Brain Mapping ◽

Single Photon ◽

Photon Emission ◽

Emission Computed Tomography ◽

Positron Emission ◽

Magnetic Resonance Imaging Mri ◽

Near Future ◽

The Brain ◽

Photon Emission Computed Tomography

Neuroimaging is traditionally divided into structural and functional imaging. Structural imaging looks at brain structure or anatomy and includes computed tomography (CT) and magnetic resonance imaging (MRI). Functional techniques seek to examine the physiological functioning of the brain, either at rest or during activation, and include single photon emission computed tomography (SPECT), positron emission tomography (PET), MRI spectroscopy, functional MRI (fMRI) and encephalographic brain mapping. Although fMRI, MRI spectroscopy and brain mapping are likely to have clinical applications in the near future, the main imaging modalities of current clinical relevance to psychiatrists are CT, MRI and SPECT, which will be the focus of this article.

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