scholarly journals A parametric model of the brain vascular system for estimation of the arterial input function (AIF) at the tissue level

2017 ◽  
Vol 30 (5) ◽  
pp. e3695 ◽  
Author(s):  
Siamak P. Nejad-Davarani ◽  
Hassan Bagher-Ebadian ◽  
James R. Ewing ◽  
Douglas C. Noll ◽  
Tom Mikkelsen ◽  
...  
Keyword(s):  
Vascular System ◽  
Arterial Input Function ◽  
Input Function ◽  
Tissue Level ◽  
Parametric Model ◽  
The Brain

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

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.

scholarly journals Optimal Scaling Approaches for Perfusion MRI with Distorted Arterial Input Function (AIF) in Patients with Ischemic Stroke

2022 ◽  
Vol 12 (1) ◽  
pp. 77
Author(s):  
Sukhdeep Singh Bal ◽  
Fan Pei Gloria Yang ◽  
Yueh-Feng Sung ◽  
Ke Chen ◽  
Jiu-Haw Yin ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Arterial Input Function ◽  
Input Function ◽  
Peak Height ◽  
Perfusion Mri ◽  
Mri Imaging ◽  
Inaccurate Estimation ◽  
Parameter Values ◽  
The Brain ◽  
Accurate Quantification

Background: Diagnosis and timely treatment of ischemic stroke depends on the fast and accurate quantification of perfusion parameters. Arterial input function (AIF) describes contrast agent concentration over time as it enters the brain through the brain feeding artery. AIF is the central quantity required to estimate perfusion parameters. Inaccurate and distorted AIF, due to partial volume effects (PVE), would lead to inaccurate quantification of perfusion parameters. Methods: Fifteen patients suffering from stroke underwent perfusion MRI imaging at the Tri-Service General Hospital, Taipei. Various degrees of the PVE were induced on the AIF and subsequently corrected using rescaling methods. Results: Rescaled AIFs match the exact reference AIF curve either at peak height or at tail. Inaccurate estimation of CBF values estimated from non-rescaled AIFs increase with increasing PVE. Rescaling of the AIF using all three approaches resulted in reduced deviation of CBF values from the reference CBF values. In most cases, CBF map generated by rescaled AIF approaches show increased CBF and Tmax values on the slices in the left and right hemispheres. Conclusion: Rescaling AIF by VOF approach seems to be a robust and adaptable approach for correction of the PVE-affected multivoxel AIF. Utilizing an AIF scaling approach leads to more reasonable absolute perfusion parameter values, represented by the increased mean CBF/Tmax values and CBF/Tmax images.

scholarly journals Arterial input function measurements for bolus tracking perfusion imaging in the brain

2012 ◽  
Vol 69 (3) ◽  
pp. 771-780 ◽  
Author(s):  
Elias Kellner ◽  
Irina Mader ◽  
Michael Mix ◽  
Daniel Nico Splitthoff ◽  
Marco Reisert ◽  
...  
Keyword(s):  
Perfusion Imaging ◽  
Arterial Input Function ◽  
Input Function ◽  
Bolus Tracking ◽  
The Brain

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

1988 ◽  
Vol 8 (1_suppl) ◽  
pp. S31-S37 ◽  
Author(s):  
James L. Lear
Keyword(s):  
Arterial Input Function ◽  
Input Function ◽  
Brain Regions ◽  
Male Rats ◽  
Type Model ◽  
Emission Computed Tomography ◽  
Intravenous Injections ◽  
Positron Emission ◽  
Uptake Pattern ◽  
The Brain

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.

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

2021 ◽  
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

Abstract Purpose Phosphodiesterase (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. Conclusion We 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.

Macroscopic Anatomy and Brain Vascularization in the Greater Rhea (Rhea americana americana)

2018 ◽  
Vol 46 (1) ◽  
Author(s):  
Herson Da Silva Costa ◽  
Hélio Norberto De Araújo Júnior ◽  
Ferdinando Vinícius Fernandes Bezerra ◽  
Carlos Eduardo Vale Rebouças ◽  
Danilo José Ayres De Menezes ◽  
...  
Keyword(s):  
Basilar Artery ◽  
Carotid Arteries ◽  
Vascular System ◽  
Cerebral Arteries ◽  
Cervical Region ◽  
Type I ◽  
Macroscopic Anatomy ◽  
Rhea Americana ◽  
Vascular Type ◽  
The Brain

 Background: The Rhea americana americana is a wild bird belonging to the group of Ratites, and is important from the scientific point of view given their adaptability to captivity. Considering that information about its morphology is important for the viability of domesticating the species, the aim of this study was to macroscopically identify the brain regions, as well as the cerebral arteries and the cerebral arterial circuit in order to establish the cerebral vascular pattern and systematization.Materials, Methods & Results: Twenty one brains from young and adult Greater Rheas of both sexes were used from animals that had died due to natural causes and were then kept in a freezer. The specimens were thawed and incised in the cervical region to allow exposure of the left common carotid artery, which was cannulated. The vascular system was rinsed with 0.9% saline solution, then perfused with latex Neoprene 650 stained with red pigment. The animals were subsequently fixed in 3.7% aqueous formaldehyde solution for 72 h, and then they were dissected by removing the bones from the skull cap. The brains were analyzed, and the structures were identified, photographed, schematized and denominated. Morphometric measurements were performed on the basilar and cerebellar ventral caudal arteries, recording the values of length and width in millimeters with the aid of a digital caliper. The brain was divided into: telencephalon, diencephalon, brainstem and cerebellum; while externally, the observed structures are: olfactory bulbs, optical lobes, optic nerves, optic chiasm, pituitary and pineal glands. Vascularization was performed by the following arteries: ventral spinal artery, basilar artery, ventricular cerebellar arteries, medium ventricular cerebellar arteries, caudal branches of the carotid arteries of the brain, ventral mesencephalic artery, cerebral caudal arteries, rostral branches of the carotid arteries of the brain, middle cerebral arteries, cerebroethmoidal arteries, rostral intercerebral anastomosis, rostral cerebral arteries, ethmoidal arteries, internal ophthalmic arteries, inter-hemispheric artery, pituitary arteries, dorsal mesencephalic tectal arteries, dorsal cerebellar arteries, occipital, pineal and dorsal hemispherical branches. The cerebral arterial circuit was both caudally and rostrally closed in 100.0% of the samples, being composed of the arteries: basilar artery, caudal branches of the carotid brain, rostral branches of the brain carotid, cerebroethmoidal arteries and rostral intercerebral anastomosis.Discussion: Encephalon classification regarding the presence or absence of gyri is a characteristic associated to evolution­ary aspects among vertebrates, being respectively considered as lisencephalon or girencecephalus when it presents or does not present convolutions. In Greater Rheas, the telencephalon was quite developed, with a relatively rounded shape and the absence of sulci and convolutions in the cortex, which allowed it to be classified as a lisencephalon. Such findings resemble those described for the ostrich and in a comparative study involving kiwis, emus, owls and pigeons, although different sizes and forms of telencephalon development were observed in the latter. Regarding the cerebral arterial circuit, this structure in Rheas was complete and both caudally and rostrally closed in 100.0% of the specimens. Our findings differ from those ob­served for ostriches, in which a rostrally open behavior has been described, while it is caudally closed in 20.0% of cases and opened in 80.0%. Regarding the vascular type of the brain, in the Rhea it was observed that there was only contribution of the carotid system, similar to that found for birds such as ostriches and turkeys which confer a type I encephalic vascularization.Keywords: arteries, brain, arterial circuit, morphometry, ratites.

scholarly journals Normative distribution of posterior circulation tissue time-to-maximum: Effects of anatomic variation, tracer kinetics, and implications for patient selection in posterior circulation ischemic stroke

2021 ◽  
pp. 0271678X2098239
Author(s):  
Adam E Goldman-Yassen ◽  
Matus Straka ◽  
Michael Uhouse ◽  
Seena Dehkharghani
Keyword(s):  
Ischemic Stroke ◽  
Selection Criteria ◽  
Arterial Input Function ◽  
Anatomic Variation ◽  
Input Function ◽  
Posterior Circulation ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Perfusion Time

The generalization of perfusion-based, anterior circulation large vessel occlusion selection criteria to posterior circulation stroke is not straightforward due to physiologic delay, which we posit produces physiologic prolongation of the posterior circulation perfusion time-to-maximum (Tmax). To assess normative Tmax distributions, patients undergoing CTA/CTP for suspected ischemic stroke between 1/2018-3/2019 were retrospectively identified. Subjects with any cerebrovascular stenoses, or with follow-up MRI or final clinical diagnosis of stroke were excluded. Posterior circulation anatomic variations were identified. CTP were processed in RAPID and segmented in a custom pipeline permitting manually-enforced arterial input function (AIF) and perfusion estimations constrained to pre-specified vascular territories. Seventy-one subjects (mean 64 ± 19 years) met inclusion. Median Tmax was significantly greater in the cerebellar hemispheres (right: 3.0 s, left: 2.9 s) and PCA territories (right: 2.9 s; left: 3.3 s) than in the anterior circulation (right: 2.4 s; left: 2.3 s, p < 0.001). Fetal PCA disposition eliminated ipsilateral PCA Tmax delays (p = 0.012). Median territorial Tmax was significantly lower with basilar versus any anterior circulation AIF for all vascular territories (p < 0.001). Significant baseline delays in posterior circulation Tmax are observed even without steno-occlusive disease and vary with anatomic variation and AIF selection. The potential for overestimation of at-risk volumes in the posterior circulation merits caution in future trials.

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