scholarly journals [11C]Flumazenil PET in Temporal Lobe Epilepsy: Do We Need an Arterial Input Function or Kinetic Modeling?

2007 ◽  
Vol 28 (1) ◽  
pp. 207-216 ◽  
Author(s):  
Alexander Hammers ◽  
Prasan Panagoda ◽  
Rolf A Heckemann ◽  
Wolfgang Kelsch ◽  
Federico E Turkheimer ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Arterial Input Function ◽  
Diagnostic Yield ◽  
Hippocampal Sclerosis ◽  
Input Function ◽  
Binding Potential ◽  
Reference Tissue ◽  
Arterial Plasma

Reduced signal on [11C]]flumazenil (FMZ) positron emission tomography (PET) is associated with epileptogenic foci. Linear correlations within individuals between parametric and nonparametric images of FMZ binding have been shown, and various methods have been used, without comparison of diagnostic usefulness. Using hippocampal sclerosis (HS) as a test case, we formally compare the diagnostic yield of parametric images obtained either with a parent tracer arterial plasma input function and spectral analysis (yielding volume-of-distribution (VD) images), or with an image-based input function and the simplified reference tissue model (binding potential images, BP-SRTM) with the diagnostic yield of semiquantitative-integrated (ADD) images from 10 to 20 or 20 to 40 mins (ADD1020 and ADD2040). Dynamic 90-min [11C]FMZ PET datasets and arterial plasma input functions were available for 15 patients with medically refractory medial temporal lobe epilepsy (TLE) and histologically verified unilateral HS and for 13 control subjects. SPM2 was used for analysis. ADD1020 and ADD2040 images showed decreased FMZ uptake ipsilateral to the epileptogenic hippocampus in 13/15 cases; 6/13 had bilateral decreases in the ADD1020 analysis and 5/13 in the ADD2040 analysis. BP-SRTM images detected ipsilateral decreases in 12/15 cases, with bilateral decreases in three. In contrast, VD images showed ipsilateral hippocampal decreases in all 15 patients, with bilateral decreases in three patients. Bilateral decreases in the ADD images tended to be more symmetrical and in one case were more marked contralaterally. Full quantification with an image-independent input should ideally be used in the evaluation of FMZ PET; at least in TLE, intrasubject correlations do not predict equivalent clinical usefulness.

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.

Inflammatory reactions in human medial temporal lobe epilepsy with hippocampal sclerosis

2002 ◽  
Vol 952 (2) ◽  
pp. 159-169 ◽  
Author(s):  
Arielle Crespel ◽  
Philippe Coubes ◽  
Marie-Claude Rousset ◽  
Corinne Brana ◽  
Alain Rougier ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Hippocampal Sclerosis ◽  
Inflammatory Reactions ◽  
Medial Temporal Lobe Epilepsy

scholarly journals Mechanisms of development of temporal lobe epilepsy: clinical and experimental studies

2002 ◽  
Vol XXXIV (1-2) ◽  
pp. 51-59
Author(s):  
O. P. Balykova ◽  
N. P. Shikhanov ◽  
V. S. Inozemtseva ◽  
A. A. Sosunov ◽  
G. McKhann ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Limbic System ◽  
Medial Temporal Lobe ◽  
Structural Changes ◽  
Hippocampal Sclerosis ◽  
Experimental Studies ◽  
Temporal Cortex ◽  
Epileptic Seizures ◽  
Clinical Effectiveness

Among the many forms of epilepsy, one of the most studied is epilepsy of the temporal lobe (temporal lobe epilepsy) associated with the pathology of the limbic system, and especially the hippocampus. Sections of the limbic system are the source of epileptic seizures in this form of the disease, which is confirmed by electroencephalographic data, including those obtained using embedded electrodes [81], and the clinical effectiveness of surgery. Removal of certain parts of the medial temporal cortex, including part of the hippocampus, can heal or reduce the frequency and severity of seizures [92]. On the basis of structural changes, two main types of epilepsy of the temporal lobe are distinguished: 1) with the presence of a volumetric process (tumor, congenital pathology, blood vessel aneurysm, hemorrhage) affecting the limbic system; 2) without the presence of clearly verified volumetric changes in the medial temporal lobe [23]. In the latter case, the only structural manifestation of temporal lobe epilepsy is hippocampal sclerosis. The name reflects the most striking morphological manifestations of the disease - the loss of neurons primarily in the CA1 and CA3 zones of the horn of the ammonia and the development of replacement gliosis. Intravital brain imaging using functional positron emission tomography, magnetic resonance imaging, and magneto-encephalography confirms changes in the hippocampus in temporal lobe epilepsy, usually in the form of a decrease in its volume [60]. There is also a positive correlation between intravital structural and biochemical (in particular, the number of AMPA-A receptors and the intensity of absorption of F-fluoro-2-deoxy-D-glucose) changes in the sclerosed hippocampus and data from the study of surgical material [75].

Auditory Temporal Ordering in Patients with Medial Temporal Lobe Epilepsy with and without Hippocampal Sclerosis

2021 ◽  
Vol 69 (2) ◽  
pp. 414
Author(s):  
AravindK Rajasekaran ◽  
Nagarajarao Shivashankar ◽  
Sanjib Sinha ◽  
Jitender Saini ◽  
DoddaballapuraK Subbakrishna ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Hippocampal Sclerosis ◽  
Medial Temporal Lobe Epilepsy ◽  
Temporal Ordering

scholarly journals Medial temporal lobe epilepsy associated with hippocampal sclerosis is a distinctive syndrome

2017 ◽  
Vol 264 (5) ◽  
pp. 875-881 ◽  
Author(s):  
Young Joo No ◽  
Chiara Zavanone ◽  
Franck Bielle ◽  
Vi-Huong Nguyen-Michel ◽  
Yves Samson ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Hippocampal Sclerosis ◽  
Medial Temporal Lobe Epilepsy

Diffusion tensor imaging in medial temporal lobe epilepsy with hippocampal sclerosis

NeuroImage ◽  
2005 ◽  
Vol 28 (3) ◽  
pp. 682-690 ◽  
Author(s):  
Lionel Thivard ◽  
Stéphane Lehéricy ◽  
Alexandre Krainik ◽  
Claude Adam ◽  
Didier Dormont ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Diffusion Tensor ◽  
Hippocampal Sclerosis ◽  
Medial Temporal Lobe Epilepsy
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