Late relapse of anti-N-methyl-d-aspartate receptor encephalitis with amusia and transiently reduced uptake in 123I-iomazenil single-photon emission computed tomography.

INTRODUCTION: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis has a high relapse rate at approximately 10-20%. Most relapses occur within 2 years from onset, and 5 years after onset is rare. We report a case of anti-NMDAR encephalitis relapse with amusia 10 years after the initial encephalitis and discuss the usefulness of 123I-iomazenil single-photon emission computerized tomography (IMZ-SPECT) for its diagnosis. CASE: A 13-year-old left-handed girl presented with a depressed level of consciousness and focal to bilateral tonic-clonic seizures. Cerebrospinal fluid (CSF) analysis showed a mildly increased white blood cell count, elevated neopterin levels, and positive oligoclonal bands. Brain MRI was normal. IMZ-SPECT revealed reduced uptake in the right frontoparietal region. She received intravenous pulse methylprednisolone (IVMP) and high-dose intravenous immunoglobulin for autoimmune encephalitis; her symptoms resolved without neurological deficits. At 23 years old, she had mild right-sided numbness, dysarthria, amusia, and tonic-clonic seizures. Although the CSF analysis and brain MRI were normal, IMZ-SPECT revealed reduced uptake, indicating a relapse of encephalitis. IVMP administration resolved the symptoms. After discharge, the initial and relapse CSF analysis revealed anti-NMDAR antibodies. CONCLUSION: An anti-NMDAR encephalitis relapse 10 years after onset has never been reported. IMZ-SPECT may help in the diagnosis of anti-NMDAR encephalitis.

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.

OBJECTIVE: 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. METHODS: Twenty-two patients who underwent indirect revascularization surgery alone also underwent brain SPECT scanning at 180 minutes after 123I-iomazenil administration and neuropsychological testing before and at 6 months after surgery. The affected-to-contralateral cerebral hemispheric asymmetry of tracer uptake before and after surgery was then calculated. RESULTS: 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. CONCLUSIONS: 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.

[123I]Iomazenil SPECT Detects a Reversible Lesion of the Left Medial Temporal Lobe in a Case of Global Autobiographical Amnesia.

Global autobiographical amnesia is a rare disorder that is characterized by a sudden loss of autobiographical memories covering many years of an individual's life. Generally, routine neuroimaging studies such as CT and MRI yield negative findings in individuals with global autobiographical amnesia. However, in recent case reports, functional analyses such as SPECT and fMRI have revealed changes in activity in various areas of the brain when compared with controls. Studies using iomazenil (IMZ) SPECT with individuals with global autobiographical amnesia have not been reported. We report the case of a 62-year-old Japanese woman with global autobiographical amnesia who had disappeared for ∼4 weeks. [123I]-IMZ SPECT showed reduced IMZ uptake in her left medial temporal lobe and no significant reduction on N-isopropyl-[123I] p-iodoamphetamine (IMP) SPECT in the identical region. Because IMZ binds to the central benzodiazepine receptor, this dissociation between IMZ and IMP SPECT was thought to reflect the breakdown of inhibitory neurotransmission in the left medial temporal lobe. Moreover, when the woman recovered most of her memory 32 months after fugue onset, the IMZ SPECT-positive lesion had decreased in size. Because the woman had long suffered verbal abuse from her former husband's sister and brother, which can also cause global autobiographical amnesia, it is difficult to conclude whether the IMZ SPECT-positive lesion in the left medial temporal lobe was the cause or the result of her global autobiographical amnesia. Although only one case, these observations suggest that IMZ SPECT may be useful in uncovering the mechanisms underlying global autobiographical amnesia.

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.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Improvement in gait function after CEA is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex.

Long-Term Outcomes of Cerebral Blood Flow and Neurotransmitter Receptor Function on Iodine-123-Iomazenil Single-Photon Emission Computed Tomography and Cognitive Assessments After Parent Artery Occlusion Combined with Cerebral Revascularization for Internal Carotid Artery Aneurysms.

OBJECTIVE: Many studies of external-internal carotid artery (EC-IC) bypass as cerebral revascularization for unclippable internal carotid artery (ICA) aneurysms have reported surgical outcomes, including bypass patency and aneurysm resolution. However, no previous studies have assessed the long-term outcomes of cerebral blood flow (CBF), brain neural density, and cognition. The purpose of the present study was to evaluate the long-term outcomes of CBF and neurotransmitter receptor function using early and late images of iodine-123 (123I)-iomazenil (IMZ) single-photon emission computed tomography (SPECT) and the cognitive function of patients who had undergone EC-IC bypass for symptomatic aneurysms in the cavernous portion of the ICA. METHODS: We performed a prospective observational study of 11 patients who had undergone superficial temporal artery-middle cerebral artery bypass or bypass using a saphenous vein graft for symptomatic aneurysms in the cavernous portion of the ICA. One patient experienced extensive infarction and, therefore, did not undergo postoperative testing. 123I-IMZ SPECT was performed with scanning at 23 minutes (early) and 180 minutes (late) after tracer administration before and after surgery. The preoperative and follow-up neuropsychological test scores from 6 patients were also analyzed. RESULTS: None of 10 patients who had undergone EC-IC bypass showed reductions in CBF and brain neural density. In addition, the neuropsychological test scores had not changed significantly from preoperatively to postoperatively. CONCLUSION: Using early and late 123I-IMZ SPECT, the present study has demonstrated that patients undergoing uncomplicated cerebral revascularization for unclippable ICA aneurysms will not experience reductions in CBF or neurotransmitter receptor function, and their cognitive function was not impaired.

Detection of Transient Increase of Cerebral Blood Flow and Reversible Neuronal Dysfunction by Iodine-123-Iomazenil Single Photon Emission Computed Tomography After Cerebral Hyperperfusion Syndrome After Revascularization Surgery for Moyamoya Disease.

BACKGROUND: Early and late images of single photon emission computed tomography (SPECT) using 123I-iomazenil (123I-IMZ) can demonstrate cerebral blood flow and cortical neuronal viability. Hyperperfusion syndrome is one of the serious complications after revascularization surgery for moyamoya disease; therefore, the real-time observation of the hemodynamics and neuronal viability is important for the treatment after the revascularization. Here we report, a case of moyamoya disease where 123I-IMZ SPECT had a significant efficacy to delineate the hemodynamics and transient neuronal dysfunction in hyperperfusion state after revascularization. CASE DESCRIPTION: A 47-year-old woman presented with motor aphasia 3 days after superficial temporal artery-middle cerebral artery anastomosis with indirect revascularization. Magnetic resonance imaging (MRI) on the same day showed no new ischemic changes but high intensities along the left frontal sulci observed on fluid-attenuated inversion recovery images, and 123I-IMZ SPECT demonstrated the increased uptake on the early images and the decreased uptake on the late images around the anastomosis site. The patient was completely recovered 1 month after surgery, and abnormal changes on MRI and 123I-IMZ SPECT returned to normal along with the symptom withdrawal. CONCLUSIONS: These findings indicate that 123I-IMZ SPECT could be the index for the treatment of revascularization for obstructive vascular diseases such as moyamoya disease.

Iodine-123-Iomazenil SPECT Revealed Recovery of Neuronal Viability in Association with Improvement in Symptoms Following Treatment for Obstructive Hydrocephalus due to a Giant Posterior Cerebral Artery Aneurysm.

BACKGROUND: Early and late images of 123I-iomazenil (123I-IMZ) single-photon emission computed tomography (SPECT) are considered to show cerebral blood flow and neuronal activity, respectively, and this modality may demonstrate temporal dysfunction of the frontal lobes in obstructive hydrocephalus. In this report, we examined 123I-IMZ SPECT in a patient with chronic obstructive hydrocephalus owing to compression of the aqueduct by a partially thrombosed aneurysm of the left posterior cerebral artery for the first time. CASE DESCRIPTION: A woman aged 77 years presented with progression of cognitive decline, gait disturbance, and urinary incontinence. She had a medical history of epilepsy and subarachnoid hemorrhage due to a ruptured left posterior cerebral artery aneurysm, treated conservatively when she was age 56 years. Magnetic resonance imaging revealed a mass lesion in the pineal region, which showed a target sign with gadolinium-based contrast agents, causing obstructive hydrocephalus owing to compression of the cerebral aqueduct. A right vertebral angiogram confirmed the presence of a partially thrombosed giant aneurysm at the left posterior cerebral artery. To rule out the involvement of nonconvulsive status epilepticus in her pathology, we performed 123I-IMZ SPECT, and both early and late images demonstrated low uptake in the bilateral frontal cortex. After surgical trapping of the parent artery and resection of the aneurysm, hydrocephalus was relieved, and the symptoms disappeared along with improvement in early and late 123I-IMZ SPECT images. CONCLUSIONS: The findings in the present case indicate that 123I-IMZ SPECT can detect reversible cerebral blood flow reduction and neuronal viability in the frontal lobes, which may affect the clinical manifestation of obstructive hydrocephalus.

Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy.

BACKGROUND: Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of this research was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG. METHODS: Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2'-[18F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BPND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ. RESULTS: Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data. CONCLUSION: Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation.

Brain pharmacology of intrathecal antisense oligonucleotides revealed through multimodal imaging.

Intrathecal (IT) delivery and pharmacology of antisense oligonucleotides (ASOs) for the CNS have been successfully developed to treat spinal muscular atrophy. However, ASO pharmacokinetic (PK) and pharmacodynamic (PD) properties remain poorly understood in the IT compartment. We applied multimodal imaging techniques to elucidate the IT PK and PD of unlabeled, radioactively labeled, or fluorescently labeled ASOs targeting ubiquitously expressed or neuron-specific RNAs. Following lumbar IT bolus injection in rats, all ASOs spread rostrally along the neuraxis, adhered to meninges, and were partially cleared to peripheral lymph nodes and kidneys. Rapid association with the pia and arterial walls preceded passage of ASOs across the glia limitans, along arterial intramural basement membranes, and along white-matter axonal bundles. Several neuronal and glial cell types accumulated ASOs over time, with evidence of probable glial accumulation preceding neuronal uptake. IT doses of anti-GluR1 and anti-Gabra1 ASOs markedly reduced the mRNA and protein levels of their respective neurotransmitter receptor protein targets by 2 weeks and anti-Gabra1 ASOs also reduced binding of the GABAA receptor PET ligand 18F-flumazenil in the brain over 4 weeks. Our multimodal imaging approaches elucidate multiple transport routes underlying the CNS distribution, clearance, and efficacy of IT-dosed ASOs.

Serum Adipokines, Growth Factors, and Cytokines Are Independently Associated with Stunting in Bangladeshi Children.

Growth in young children is controlled through the release of several hormonal signals, which are affected by diet, infection, and other exposures. Stunting is clearly a growth disorder, yet limited evidence exists documenting the association of different growth biomarkers with child stunting. This study explored the association between different growth biomarkers and stunting in Bangladeshi children. A quasi-experimental study was conducted among 50 stunted (length-for-age Z-score (LAZ) < -2 SD) and 50 control (LAZ ≥ -2 SD) children, aged 12-18 months, residing in a Bangladeshi slum. The enrolled stunted children received an intervention package, which included food supplementation for three months, psychosocial stimulation for six months, and routine clinical care on community nutrition center at the study field site. The controls received routine clinical care only. All children were clinically screened over the study period. Length, weight, fasting blood and fecal biomarkers were measured. All biomarkers levels were similar in both groups except for oxyntomodulin at enrolment. Leptin (adjusted odds ratio, AOR: 4.0, p < 0.01), leptin-adiponectin ratio (AOR 5.07 × 108, p < 0.01), insulin-like growth factor-1 (IGF-1) (AOR 1.02, p < 0.05), and gamma interferon (IFN-γ) (AOR 0.92, p < 0.05) levels were independently associated with stunting at enrolment. Serum leptin, leptin-adiponectin ratio, interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), and fecal alpha-1-antitrypsin (AAT) levels increased significantly (p < 0.001), while IFN-γ levels significantly decreased among stunted children after six months of intervention. Leptin, leptin-adiponectin ratio, IGF-1, and IFN-γ are independently associated with stunting in Bangladeshi children. This trial was registered at clinicaltrials.gov as NCT02839148.

[123I-Iomazenil Single-Photon Emission Computed Tomography Imaging in a Patient with Mild Traumatic Subdural Hematoma Accompanied by Delayed Transient Aphasia].

Early and late images of 123I-iomazenil(IMZ)single-photon emission computed tomography(SPECT)reflect distributions of cerebral blood flow and those of cortical benzodiazepine receptor binding potential, respectively. Crossed cerebellar diaschisis reflects left-to-right asymmetry of metabolism in the cerebral hemispheres. We present a case of a 67-year-old woman who developed transient aphasia 3 days after the onset of a mild acute subdural hematoma. Computed tomography scan and magnetic resonance imaging during aphasia did not show enlargement of the hematoma or any new lesions. Electroencephalography did not show any abnormalities. Early images of 123I-IMZ SPECT 3 days after the onset of aphasia revealed a decrease in radioactivity in the right cerebellar hemisphere relative to that in the left cerebellar hemisphere. Late images of the same 123I-IMZ SPECT displayed a decrease in radioactivity in the left cerebral hemisphere relative to that in the right cerebral hemisphere. Twenty-four days later, the aphasia disappeared and the left-to-right asymmetries of radioactivity in the cerebellar and cerebral hemispheres on the early and late 123I-IMZ SPECT images also resolved.

Dynamic image denoising for voxel-wise quantification with Statistical Parametric Mapping in molecular neuroimaging.

PURPOSE: PET and SPECT voxel kinetics are highly noised. To our knowledge, no study has determined the effect of denoising on the ability to detect differences in binding at the voxel level using Statistical Parametric Mapping (SPM). METHODS: In the present study, groups of subject-images with a 10%- and 20%- difference in binding of [123I]iomazenil (IMZ) were simulated. They were denoised with Factor Analysis (FA). Parametric images of binding potential (BPND) were produced with the simplified reference tissue model (SRTM) and the Logan non-invasive graphical analysis (LNIGA) and analyzed using SPM to detect group differences. FA was also applied to [123I]IMZ and [11C]flumazenil (FMZ) clinical images (n = 4) and the variance of BPND was evaluated. RESULTS: Estimations from FA-denoised simulated images provided a more favorable bias-precision profile in SRTM and LNIGA quantification. Simulated differences were detected in a higher number of voxels when denoised simulated images were used for voxel-wise estimations, compared to quantification on raw simulated images. Variability of voxel-wise binding estimations on denoised clinical SPECT and PET images was also significantly diminished. CONCLUSION: In conclusion, noise removal from dynamic brain SPECT and PET images may optimize voxel-wise BPND estimations and detection of biological differences using SPM.

Double match of 18F-fluorodeoxyglucose-PET and iomazenil-SPECT improves outcomes of focus resection surgery.

BACKGROUND: When the results of electroencephalography (EEG), magnetic resonance imaging (MRI), and seizure semiology are discordant or no structural lesion is evident on MRI, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are important examinations for lateralization or localization of epileptic regions. We hypothesized that the concordance between interictal 2-[18F]fluoro-2-deoxy-D-glucose (18FDG)-PET and iomazenil (IMZ)-SPECT could suggest the epileptogenic lobe in patients with non-lesional findings on MRI. METHOD: Fifty-nine patients (31 females, 28 males; mean age, 29 years; median age, 27 years; range, 7-56 years) underwent subdural electrode implantation followed by focus resection. All patients underwent 18FDG-PET, IMZ-SPECT, and focus resection surgery. Follow-up was continued for ≥ 2 years. We evaluated surgical outcomes as seizure-free or not and analyzed correlations between outcomes and concordances of low-uptake lobes on PET, SPECT, or both PET and SPECT to the resection lobes. We used uni- and multivariate logistic regression analyses. RESULTS: In univariate analyses, all three concordances correlated significantly with seizure-free outcomes (PET, p = 0.017; SPECT, p = 0.030; both PET and SPECT, p = 0.006). In multivariate analysis, concordance between resection and low-uptake lobes in both PET and SPECT correlated significantly with seizure-free outcomes (p = 0.004). The odds ratio was 6.0. CONCLUSION: Concordance between interictal 18FDG-PET and IMZ-SPECT suggested that the epileptogenic lobe is six times better than each examination alone among patients with non-lesional findings on MRI. IMZ-SPECT and 18FDG-PET are complementary examinations in the assessment of localization-related epilepsy.

123I-iomazenil whole-body imaging to detect hepatic carboxylesterase drug-metabolizing enzyme activity.

OBJECTIVES: Drugs are mainly metabolized by hepatic enzymes, the activity of which can differ between individuals. Although it is ideal to measure the hepatic clearance of liver-targeted drugs in individualized medicine, blood enzyme tests typically measure metabolic drug clearance in the entire body, and not just in the liver. We investigated whether I-iomazenil imaging can directly assess and quantify the activity of hepatic drug-metabolizing enzymes. MATERIALS AND METHODS: Hepatic enzymes that metabolize I-iomazenil were identified by thin-layer chromatography in mouse liver homogenates with bis(4-nitrophenyl) phosphate (BNPP) inhibitor for carboxylesterase enzymes and nicotinamide adenine dinucleotide phosphate (NADPH) generator for cytochrome P450 enzymes. Whole-body images of mice were acquired using I-iomazenil with and without BNPP, and the distribution was also obtained. The metabolism of I-iomazenil in the blood, liver, gall bladder, and bladder was investigated by thin-layer chromatography. RESULTS: From the in-vitro metabolism of I-iomazenil using BNPP, the enzyme converting I-iomazenil to I-R-COOH was identified as carboxylesterase, and that converting I-iomazenil to M2 was identified as cytochrome P450 in experiments with and without an NADPH generator. The biological distribution and whole-body imaging showed increased accumulation in the liver of mice administered BNPP compared with normal mice, but decreased levels in the gall bladder and small intestine. The main fraction in bile and urine was I-R-COOH, with two unknown metabolites (M1 and M2), I, and I-iomazenil also being present. CONCLUSION: I-iomazenil whole-body imaging has good possibility of direct measurement of hepatic carboxylesterase activity as accumulation of I-R-COOH in the gall bladder through bile and in the bladder through urine.

Maturational Changes of Gamma-Aminobutyric Acid A Receptors Measured With Benzodiazepine Binding of Iodine 123 Iomazenil Single-Photon Emission Computed Tomography.

BACKGROUND: Iodine 123 (I-123) iomazenil is a specific ligand of the central benzodiazepine receptor, which is a part of the postsynaptic gamma-aminobutyric acid A receptor complex. We performed statistical image processing of I-123 iomazenil single-photon emission computed tomography to elucidate maturational changes in the GABAergic system. METHODS: Thirty patients (18 boys and 12 girls, aged 17 days to 14 years) with cryptogenic focal epilepsy were enrolled and underwent I-123 iomazenil single-photon emission computed tomography. We used a semiquantitative analytical method consisting of brain surface extraction, anatomic normalization, and a three-parameter exponential model. We then assessed developmental changes in benzodiazepine receptor binding activity in 18 regions of interest in both hemispheres. RESULTS: The highest benzodiazepine receptor binding activity was observed during early infancy in all regions of interest. Benzodiazepine receptor binding activity then decreased exponentially across development. Benzodiazepine receptor binding in the primary sensorimotor cortex, primary visual cortex, cerebellar vermis, and striatum declined more rapidly than that in the cerebellar hemispheres and the frontal cortex. The pons and the thalamus had the lowest benzodiazepine receptor binding activities during the neonatal period, and benzodiazepine receptor binding in these areas declined gradually after infancy toward adolescence. There were no differences in adjusted benzodiazepine receptor binding activity according to laterality or sex. CONCLUSIONS: Benzodiazepine receptor binding activity decreased exponentially during infancy in all regions of interest. Binding activity in the primary somatosensory and motor cortices (M1 and S1), the primary and association visual areas, the cerebellar vermis, and the striatum (caudate nucleus and putamen) tended to decline more rapidly than that in the cerebellar hemisphere and the frontal association cortex.

Crossed Cerebellar Tracer Uptake on Acute-Stage 123I-Iomazenil SPECT Imaging Predicts 3-Month Functional Outcome in Patients With Nonfatal Hypertensive Putaminal or Thalamic Hemorrhage.

PURPOSE: Whereas SPECT images obtained 180 minutes after administration of I-iomazenil (IMZ) (late images) are proportional to the distribution of central benzodiazepine receptor-binding potential, SPECT images obtained within 30 minutes after I-IMZ administration (early images) correlate with regional brain perfusion. The aim of the present study was to determine whether crossed cerebellar tracer uptake on acute-stage I-IMZ SPECT imaging predicts 3-month functional outcome in patients with nonfatal hypertensive putaminal or thalamic hemorrhage. METHODS: Forty-six patients underwent early and late SPECT imaging with I-IMZ within 7 days after the onset of hemorrhage. A region of interest was automatically placed in the bilateral cerebellar hemispheres using a 3-dimensional stereotaxic region-of-interest template, and the ratio of the value in the cerebellar hemisphere contralateral to the affected side to that in the ipsilateral cerebellar hemisphere (ARcbl) was calculated in each patient. Each patient's physical function was measured using the modified Rankin scale (mRS) score 3 months after onset. RESULTS: The ARcbl on early (ρ = -0.511, P = 0.0003) and late (ρ = -0.714, P < 0.0001) images correlated with the mRS 3 months after the onset of hemorrhage. Multivariate analysis showed that only a low ARcbl in late images was significantly associated with a poor functional outcome (mRS score ≥3 at 3 months after onset) (95% confidence interval, 0.001-0.003; P = 0.0212). CONCLUSIONS: Crossed cerebellar tracer uptake on acute-stage I-IMZ SPECT imaging predicts 3-month functional outcome in patients with nonfatal hypertensive putaminal or thalamic hemorrhage.

Increase in extraction of I-123 iomazenil in patients with chronic cerebral ischemia.

BACKGROUND: Cerebral extraction of diffusively distributed substances like oxygen has been suggested to change according to the cerebral blood flow (CBF) and status of the microvasculature. The relationships between the cerebral extraction of diffusively distributed lipophilic tracers and the severity of cerebral ischemia has not yet been clarified. In the present study, we attempted to elucidate the association between the extraction fraction of the lipophilic tracer I-123 iomazenil (IMZ) (IMZ-EF) and the oxygen extraction fraction (OEF) derived from O-15 PET in patients with chronic steno-occlusive disease of internal carotid artery (ICA) or middle cerebral artery (MCA). METHODS: Seven patients with unilateral chronic severe stenosis or occlusion of the middle cerebral/internal cerebral artery were prospectively recruited for this study. All the patients underwent both O-15 PET and quantitative I-123 IMZ SPECT. Parametric images derived from the PET and SPECT scans were anatomically normalized and evaluated by automated image analysis based on the volume-of-interest template. RESULTS: The asymmetry index (AI) of IMZ-EF was shown to be significantly correlated with the AI of OEF (r = 0.562, P < 0.001) in the internal carotid artery perfusion area. Strong and significant correlation between the AI of the influx rate constant K1 of IMZ and the AI of the cerebral metabolic rate of oxygen (r = 0.552, P = 0.001) was clarified. CONCLUSIONS: Our results suggested that the transportation efficiency of I-123 IMZ into the brain tissue was an indicator for evaluating severity of cerebral ischemia in patients with chronic steno-occlusive disease of ICA or MCA. Cerebral metabolic state can possibly be estimated by I-123 IMZ SPECT without cyclotron.

Abnormal distribution of GABAA receptors in brain of duchenne muscular dystrophy patients.

INTRODUCTION: In this study we sought to: (1) determine the distribution of GABAA receptors (GABAA -Rs) in the brain of Duchenne muscular dystrophy (DMD) patients; and (2) ascertain if the distribution pattern correlates with cognitive dysfunction. METHODS: Fourteen DMD patients [young adult (n = 7, 18-25 years old) and older adult (n = 7, 30-37 years old) groups] and 16 age-matched normal volunteers participated. GABAA -R distribution was assessed using 123 I-IMZ-SPECT. Neuropsychological assessments were performed using 3 different test batteries, the WAIS-III, WMS-R, and Wisconsin Card Sorting Test (WCST). RESULTS: All DMD patients showed significant decline in 123 I-IMZ uptake in the prefrontal cortex (P < 0.05). Although no differences were detected in the WAIS-III and WMS-R, the WCST scores of DMD patients (2.8 ± 1.9) were significantly lower (P < 0.01) than those of normal volunteers (5.4 ± 0.7). Both abnormalities were more pronounced in older adult patients. CONCLUSION: The findings demonstrate that DMD is accompanied by a reduction in the prefrontal cortex distribution of GABAA -Rs. Muscle Nerve 55: 591-595, 2017.

Histological Underpinnings of Grey Matter Changes in Fibromyalgia Investigated Using Multimodal Brain Imaging.

Chronic pain patients present with cortical gray matter alterations, observed with anatomical magnetic resonance (MR) imaging. Reduced regional gray matter volumes are often interpreted to reflect neurodegeneration, but studies investigating the cellular origin of gray matter changes are lacking. We used multimodal imaging to compare 26 postmenopausal women with fibromyalgia with 25 healthy controls (age range: 50-75 years) to test whether regional gray matter volume decreases in chronic pain are associated with compromised neuronal integrity. Regional gray matter decreases were largely explained by T1 relaxation times in gray matter, a surrogate measure of water content, and not to any substantial degree by GABAA receptor concentration, an indirect marker of neuronal integrity measured with [18F] flumazenil PET. In addition, the MR spectroscopy marker of neuronal viability, N-acetylaspartate, did not differ between patients and controls. These findings suggest that decreased gray matter volumes are not explained by compromised neuronal integrity. Alternatively, a decrease in neuronal matter could be compensated for by an upregulation of GABAA receptors. The relation between regional gray matter and T1 relaxation times suggests decreased tissue water content underlying regional gray matter decreases. In contrast, regional gray matter increases were explained by GABAA receptor concentration in addition to T1 relaxation times, indicating perhaps increased neuronal matter or GABAA receptor upregulation and inflammatory edema. By providing information on the histological origins of cerebral gray matter alterations in fibromyalgia, this study advances the understanding of the neurobiology of chronic widespread pain. SIGNIFICANCE STATEMENT: Regional gray matter alterations in chronic pain, as detected with voxel-based morphometry of anatomical magnetic resonance images, are commonly interpreted to reflect neurodegeneration, but this assumption has not been tested. We found decreased gray matter in fibromyalgia to be associated with T1 relaxation times, a surrogate marker of water content, but not with GABAA receptor concentration, a surrogate of neuronal integrity. In contrast, regional gray matter increases were partly explained by GABAA receptor concentration, indicating some form of neuronal plasticity. The study emphasizes that voxel-based morphometry is an exploratory measure, demonstrating the need to investigate the histological origin of gray matter alterations for every distinct clinical entity, and advances the understanding of the neurobiology of chronic (widespread) pain.