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

In bolus-tracking perfusion magnetic resonance imaging (MRI), temporal dispersion of the contrast bolus due to stenosis or collateral supply presents a significant problem for accurate perfusion quantification in stroke. One means to reduce the associated perfusion errors is to deconvolve the bolus concentration time-course data with local Arterial Input Functions (AIFs) measured close to the capillary bed and downstream of the arterial abnormalities causing dispersion. Because the MRI voxel resolution precludes direct local AIF measurements, they must be extrapolated from the surrounding data. To date, there have been no published studies directly validating these local AIFs. We assess the effectiveness of local AIFs in reducing dispersion-induced perfusion error by measuring the residual dispersion remaining in the local AIF deconvolved perfusion maps. Two approaches to locating the local AIF voxels are assessed and compared with a global AIF deconvolution across 19 bolus-tracking data sets from patients with stroke. The local AIF methods reduced dispersion in the majority of data sets, suggesting more accurate perfusion quantification. Importantly, the validation inherently identifies potential areas for perfusion underestimation. This is valuable information for the identification of at-risk tissue and management of stroke patients.

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

NMR in Biomedicine ◽

10.1002/nbm.3695 ◽

2017 ◽

Vol 30 (5) ◽

pp. e3695 ◽

Cited By ~ 6

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

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Quantitative myocardial perfusion imaging using a step arterial-input function

Journal of Cardiovascular Magnetic Resonance ◽

10.1186/1532-429x-18-s1-o11 ◽

2016 ◽

Vol 18 (Suppl 1) ◽

pp. O11

Author(s):

Richard B Thompson ◽

Justin Grenier ◽

Emer Sonnex ◽

Richard Coulden

Keyword(s):

Myocardial Perfusion Imaging ◽

Myocardial Perfusion ◽

Perfusion Imaging ◽

Arterial Input Function ◽

Input Function ◽

Quantitative Myocardial Perfusion

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

Brain Sciences ◽

10.3390/brainsci12010077 ◽

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.

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Comparison of arterial input function models for small-animal ultrasound perfusion imaging

2016 IEEE International Ultrasonics Symposium (IUS) ◽

10.1109/ultsym.2016.7728503 ◽

2016 ◽

Author(s):

Martin Mezl ◽

Radovan Jirik ◽

Lenka Dvorakova ◽

Eva Drazanova ◽

Radim Kolar

Keyword(s):

Perfusion Imaging ◽

Arterial Input Function ◽

Small Animal ◽

Input Function ◽

Function Models

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

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1988.30 ◽

1988 ◽

Vol 8 (1_suppl) ◽

pp. S31-S37 ◽

Cited By ~ 11

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.

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