123I-iomazenil Single Photon Emission Computed Tomography Research Articles

Recovery of Cortical Neurotransmitter Receptor Function and Its Impact on Cognitive Improvement after Indirect Revascularization Surgery Alone for Adult Patients with Ischemic Moyamoya Disease: 123I-Iomazenil Single-Photon Emission Computed Tomography Study

Brain 123I-iomazenil single-photon emission computed tomography (SPECT) can assess the distribution of the binding potential of central benzodiazepine receptors in the cerebral cortex. This binding potential may reflect neuronal function in viable tissues. The present prospective study using brain 123I-iomazenil SPECT aimed to determine whether improvements in cognitive function after indirect revascularization surgery alone are associated with postoperative recovery in neurotransmitter receptor function in the affected cerebral hemisphere among adult patients with moyamoya disease accompanied by ischemic presentation due to misery perfusion. Twenty-two patients who underwent indirect revascularization surgery alone also underwent brain SPECT scanning at 180minutes after 123I-iomazenil administration and neuropsychological testing before and at 6months after surgery. The affected-to-contralateral cerebral hemispheric asymmetry of tracer uptake before and after surgery was then calculated. The asymmetry of tracer uptake was significantly increased after surgery (P<0.0001). A significant difference between the preoperative and postoperative asymmetry of tracer uptake was seen in patients with improved cognition compared with those with unchanged cognition (P=0.0001). The area under the receiver operating characteristic curve was 0.99 for the difference between the preoperative and postoperative asymmetry of tracer uptake to assess the ability to discriminate patients with improved cognition from those with unchanged cognition. Improvements in cognitive function after indirect revascularization surgery alone are associated with postoperative recovery in the binding potential of central benzodiazepine receptors in the affected cerebral hemisphere in adult patients with moyamoya disease accompanied by ischemic presentation due to misery perfusion.

Improvement in gait function after carotid endarterectomy is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex: a 123I-iomazenil SPECT study.

Carotid endarterectomy (CEA) often restores cerebral perfusion and neurotransmitter receptor function, which is seen on early and late images, respectively, on brain I-iomazenil single-photon emission computed tomography (SPECT). The reliability of gait-related parameters obtained using a triaxial accelerometer, a portable device for gait assessment, has been confirmed with test-retest measurements. The purpose of the present prospective cohort study was to determine whether improvement in gait function after CEA is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex. Gait testing using a triaxial accelerometer was performed preoperatively and 6 months postoperatively in 64 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≥70%). I-iomazenil SPECT was also performed with scanning within 30 min (early images) and at 180 min (late images) after tracer administration before and after surgery. SPECT data were analyzed using a three-dimensional stereotactic surface projection, and motor (Brodmann 4) and premotor (Brodmann 6) cortexes in each hemisphere were combined and defined as the motor-related cortex. Based on preoperative and postoperative gait testing, seven patients (11%) showed postoperative improved gait. Logistic regression analysis revealed that postoperative increase in I-iomazenil uptake in the motor-related cortex ipsilateral to surgery on early [95% confidence interval (CI), 4.32-365.21; P = 0.0477) or late (95% CI, 9.45-1572.57; P = 0.0173) images was an independent predictor of postoperative improved gait. Improvement in gait function after CEA is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex.

Unique Distribution of Benzodiazepine Receptors in the Brain during the First Two Years of Life

Background: ¹²³I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) is a tool for evaluating epileptic foci and brain damage. To apply the method to children, information regarding the age-specific expression of benzodiazepine receptors (BDZ-Rs) is required. Unfortunately, there is no information currently available for children <2 years of age. Methods: We used IMZ SPECT once in infants aged 3-8 months and again at 2 years of age in order to describe the maturational changes in BDZ-R distribution. Results: No neurological deficits were found in any of the infants at the first examination. The BDZ-Rs were more dominantly distributed in the occipital lobe than in the frontal lobe before the age of 2 years. The frontal-occipital gradients of the distribution were obvious in children <8 months of age. Magnetic resonance imaging showed a spreading of myelination toward the frontal lobes simultaneously with BDZ-R expression. Conclusion: Information regarding the alteration in the BDZ-R distribution pattern is useful when assessing infantile epilepsy and brain injury. The age-related pattern of BDZ-R distribution could correspond with myelination, cerebral blood flow, metabolism and behavioral development.

Upregulated GABA Inhibitory Function in ADHD Children with Child Behavior Checklist-Dysregulation Profile: 123I-Iomazenil SPECT Study.

The child behavior checklist–dysregulation profile (CBCL–DP) refers to a pattern of elevated scores on the attention problems, aggression, and anxiety/depression subscales of the child behavior checklist. The aim of the present study was to investigate the potential role of GABA inhibitory neurons in children with attention deficit/hyperactivity disorder (ADHD) and dysregulation assessed with a dimensional measure. Brain single photon emission computed tomography (SPECT) was performed in 35 children with ADHD using 123I-iomazenil, which binds with high affinity to benzodiazepine receptors. Iomazenil binding activities were assessed with respect to the presence or absence of a threshold CBCL–DP (a score ≥210 for the sum of the three subscales: Attention Problems, Aggression, and Anxiety/Depression). We then attempted to identify which CBCL–DP subscale explained the most variance with respect to SPECT data, using “age,” “sex,” and “history of maltreatment” as covariates. Significantly higher iomazenil binding activity was seen in the posterior cingulate cortex (PCC) of ADHD children with a significant CBCL–DP. The Anxiety/Depression subscale on the CBCL had significant effects on higher iomazenil binding activity in the left superior frontal, middle frontal, and temporal regions, as well as in the PCC. The present brain SPECT findings suggest that GABAergic inhibitory neurons may play an important role in the neurobiology of the CBCL–DP, in children with ADHD.

Statistical parametric mapping of interictal 123I-iomazenil SPECT in temporal lobe epilepsy surgery

Brain single photon emission computed tomography (SPECT) for epilepsy is divided into two types (using three radionuclide tracers)-perfusion SPECT (123I-IMP or 99 mTc-ECD), identifying epileptogenic foci by detecting abnormality in regional cerebral blood flow, and 123I-iomazenil SPECT, identifying epileptogenic foci based on distribution of central benzodiazepine receptors. This study aimed to statistically evaluate and compare the SPECT effectiveness for the three tracers. Statistical parametric mapping (SPM) analysis was performed on 30 mesial temporal lobe epilepsy (mTLE) patients. The radionuclide and patient data were categorized as follows: abnormality in the medial temporal lobe on the operated hemisphere (AAA), in the entire temporal lobe on the operated hemisphere (AA), in the dominantly affected temporal lobe on the operated hemisphere (A), in bilateral temporal lobes (B), with no abnormalities in bilateral temporal lobes (C), and with abnormality in the temporal lobe on the nonoperated hemisphere (D). For analyses of (AAA), (AA), and (A), examining the hemisphere containing epileptogenic foci, IMP-SPECT was significantly superior to ECD-SPECT (P<0.05). For (AAA), indicating localization, IMZ-SPECT was significantly superior to the other two (P<0.05). IMP-SPECT was superior for lateralizing and IMZ-SPECT was useful for localizing epileptogenic foci in mTLE patients though the applicability of the results in extratemporal lobe epilepsy is unknown.

Comparison of early and late images on 123I-iomazenil SPECT with cerebral blood flow and oxygen extraction fraction images on PET in the cerebral cortex of patients with chronic unilateral major cerebral artery occlusive disease

The aim of the present study was to determine whether early and late/early images on 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) correlate with cerebral blood flow (CBF) images and oxygen extraction fraction (OEF) images on PET, respectively, in the cerebral cortex of patients with chronic unilateral middle cerebral artery or internal carotid artery occlusive disease. In 20 normal individuals and in 68 patients, CBF and OEF were assessed using 15O-PET, and brain SPECT scans were initiated immediately after (early images) and 180 min after (late images) the administration of 123I-IMZ. A region of interest was automatically placed in the middle cerebral artery territory in both cerebral hemispheres using a three-dimensional stereotaxic region of interest template, and the ratio of the value in the affected side to that in the contralateral side was calculated in each image. Among patients, a significant positive correlation was observed between PET-CBF ratios and the SPECT-early IMZ ratios (r=0.797, P<0.0001) as well as between the PET-OEF ratios and the SPECT-late/early IMZ ratios (r=0.679, P<0.0001). When an abnormally elevated PET-OEF ratio was defined as a value greater than the mean+2 SD obtained in normal participants, the SPECT-late/early IMZ ratios yielded 100% sensitivity and 93% specificity, with 76% positive-predictive and 100% negative-predictive values for detecting abnormally elevated PET-OEF ratios. Early and late/early images on 123I-IMZ SPECT correlate with CBF images and OEF images on PET, respectively, in the cerebral cortex of patients with chronic unilateral major cerebral artery occlusive disease.

Combination of Preoperative Cerebral Blood Flow and 123I-Iomazenil SPECT Imaging Predicts Postoperative Cognitive Improvement in Patients Undergoing Uncomplicated Endarterectomy for Unilateral Carotid Stenosis

The purpose of the present study was to determine whether preoperative cerebral blood flow (CBF) or cortical central benzodiazepine receptor binding potential as measured by brain perfusion or (123)I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) imaging, respectively, can predict cognitive improvement after uncomplicated carotid endarterectomy (CEA). Neuropsychological testing was performed preoperatively and after 1 month postoperatively in 140 patients who underwent CEA for unilateral internal carotid artery (ICA) stenosis (≥ 70%). Brain perfusion SPECT using N-isopropyl-p-[(123)I]-iodoamphetamine and IMZ SPECT was also performed before surgery. SPECT data were analyzed using a 3-dimensional stereotaxic region-of-interest template. Fourteen patients (10%) showed improved cognitive function postoperatively. Logistic regression analysis demonstrated that, among the variables tested, low relative CBF in the cerebral hemisphere ipsilateral to surgery was significantly associated with postoperative cognitive improvement (95% confidence interval: 0.623-0.868; P = 0.0003). The combination of reduced relative CBF and moderately reduced relative uptake of IMZ identified development of postoperative cognitive improvement with 100.0% sensitivity, 84.9% specificity, a positive predictive value of 42.4%, and a negative predictive value of 100%. Further, in a subgroup of patients with reduced relative CBF and moderately reduced relative uptake of IMZ, the difference between these 2 values was significantly greater in patients with postoperative cognitive improvement than in those without (P < 0.0001). The combination of preoperative CBF and cortical central benzodiazepine receptor binding potential as determined by SPECT can predict cognitive improvement after CEA.

SPECT revealed cortical dysfunction in a patient who had genetically definite megalencephalic leukoencephalopathy with subcortical cysts

We describe the findings on single photon emission computed tomography (SPECT) in a patient who had genetically definite megalencephalic leukoencephalopathy with subcortical cysts. Technetium-99m-ethyl cysteinate dimer SPECT revealed hypoperfusion in the cerebral white matter, which had shown high signal intensity on magnetic resonance imaging (MRI) T2 images. Hypoperfusion was also unexpectedly found in the frontal cortices, which showed no abnormalities on MRI. This frontal abnormality corresponded clinically to a low score on the frontal assessment battery. Decreased GABA receptor density as suggested by 123I-Iomazenil SPECT provided further evidence of cortical neuron dysfunction. Although confirmation must await future larger-scale SPECT and functional studies, our findings suggest that SPECT can be used to non-invasively monitor in vivo cortical function in this disease.

Pre-surgical identification of epileptogenic areas in temporal lobe epilepsy by 123I-iomazenil SPECT: A comparison with IMP SPECT and FDG PET

The aim of this study was to evaluate the usefulness of (123)I-iomazenil (IMZ) single photon emission computed tomography (SPECT) for the pre-surgical identification of epileptogenic areas in patients with temporal lobe epilepsy and to compare the results with those of (123)I-IMP SPECT and (18)Fluorodeoxyglucose positron emission tomography (FDG PET). We examined seven patients with medically refractory temporal lobe epilepsy (five men and two women; mean age, 28 years) with no remarkable findings on magnetic resonance imaging. Before surgery, IMZ SPECT, IMP SPECT and FDG PET were all performed in the interictal state. Then, visual assessment and region-of-interest (ROI) analysis were performed on each image. Final definitions of the epileptogenic areas were made by electrocorticography and histopathology. By IMZ SPECT, a decreased IMZ uptake in the ipsilateral temporal lobe was found in all patients, while a similar decrease in the contralateral temporal lobe was also found in one patient. In comparison to IMP SPECT, the extent of the abnormal area on IMZ SPECT was equal to that on IMP SPECT in one patient while it was more restricted to the epileptogenic area in five patients. In comparison to FDG PET, the extent of the abnormal area on IMZ SPECT was equal to that on FDG PET in three patients while it was more restricted in the epileptogenic area in four patients. In ROI analysis, decreases of IMZ, IMP and FDG uptake were observed in the epileptogenic area, although they were not statistically significant. IMZ SPECT was considered to be useful for pre-surgical determination of the epileptogenic areas in temporal lobe epilepsy with no remarkable MRI findings, and it was also found to be superior to IMP SPECT and FDG PET for this purpose.

Quantification of central benzodiazepine receptor binding potential in the brain with 123I-iomazenil SPECT: technical and interobserver variability.

Factors contributing to the quantification of the central benzodiazepine receptor binding potential in vivo using 123I-iomazenil and single photon emission computed tomography (SPECT) were analysed in phantom studies and in volunteers. SPECT was performed with the SME810 multidetector system. The Hoffman three-dimensional brain phantom was used to investigate linearity and reproducibility of SPECT results using different 123I activity concentrations. Dynamic and multislice SPECT scans were performed in nine healthy volunteers between 0 and 270 min after injection of 110 MBq 123I-iomazenil. Displacement studies were performed in three volunteers using 1 mg flumazenil administered intravenously (i.v.) at 250 min postinjection (p.i.). Regions of interest (ROIs) over the cerebral cortex and various subcortical nuclei were either fixed areas based on a stereotaxic brain atlas, or manually drawn, based on 60% isocontour lines. Interobserver variability of the ROI data and ratios derived from those data were estimated for two independent observers. The brain phantom measurements showed linearity with respect to 123I concentration and good reproducibility. The interobserver study showed a reasonable interobserver reliability for the large fixed ROIs. The displacement study showed about 50% displacement in all ROIs. Concentrations of 123I-iomazenil in the brain can be measured reliably with the SME810. Large fixed ROIs based on a stereotaxic atlas may be used reliably for quantification. The level of 4 cm above the cantomeatal line does not provide a useful reference region with a very low central benzodiazepine receptor binding potential.

Lack of effect of concomitant clobazam on interictal 123I-iomazenil SPECT

Single photon emission computed tomography (SPECT) is being increasingly used as an adjunctive technique in the localisation of epileptogenic foci prior to surgery. Fourteen patients (five male, nine female; mean age 31 years) with refractory complex partial seizures, all of whom had abnormal 99Tc HM-PAO SPECT scans, were imaged again using the benzodiazepine receptor ligand 123I-iomazenil. Eleven of these patients displayed the same abnormality on both scans. The magnitude of the deficit, however, was slightly greater ( P <0.05) on the iomazenil scan compared with the HM-PAO study. These 11 patients were then randomised into two groups. Group 1 (n = 7) received clobazam 20 mg/day for a minimum of 7 days before a second iomazenil study was performed. Patients in group 2 (n = 4) underwent a second iomazenil scan at the same time interval as those in group 1, but without the additional clobazam. The resultant scans were reported blind to treatment. There were no qualitative or quantitative differences between the first and second iomazenil studies in either group. Patients can be imaged using 123I-iomazenil without withdrawing clobazam therapy. From this preliminary study, there seems little advantage in using iomazenil in place of HM-PAO to delineate the extent of the zone of epileptogenesis. Whether iomazenil SPECT will prove to be more sensitive in identifying the site of the epileptic focus remains to be determined.