Fluorodeoxyglucose F18 positron emission tomography in a case of slowly progressive pure alexia

We describe a 71-year-old patient with slowly progressive pure alexia in which analysis of her fluorodeoxyglucose FDG-PET scan revealed an area of focal hypometabolism in the visual word form area. She presented with difficulty reading. Examination revealed pure alexia with preservation of other cognitive domains. Brain MRI revealed only slight atrophy. A Fluorodeoxyglucose F18 positron emission tomography scan revealed hypometabolism in the occipital cortex bilaterally, left greater than right, with normal metabolism elsewhere in the brain. This case highlights the utility of FDG-PET scan in evaluating focal neurodegenerative conditions before clear atrophy can be seen on MRI.     

Correlation of brain cell glucose metabolism and patient's condition in children with epileptic encephalopathy An assessment using fluorine-18-fluoro-2-deoxy-D-glucose positron emission computed tomography

We examined a total of 16 children with epileptic encephalopathy using fluo-rine-18-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission computed tomography (PET), magnetic resonance imaging (MRI) and electroencephalography. Children with infantile spasms showed significant mental retardation, severely abnormal electroencephalogram recordings, and bilateral diffuse cerebral cortex hypometabolism with 18F-FDG PET imaging. MRI in these cases showed brain atrophy, multi-micropolygyria, macrogyria, and porencephalia. In cases with Len-nox-Gastaut syndrome, 18F-FDG PET showed bilateral diffuse glucose hypometabolism, while MRI showed cortical atrophy, heterotopic gray matter and tuberous sclerosis. MRI in cases with myoclonic encephalopathy demonstrated bilateral frontal and temporal cortical and white matter atrophy and 18F-FDG PET imaging showed bilateral frontal lobe atrophy with reduced bilateral frontal cortex, occipital cortex, temporal cortex and cerebellar glucose uptake. In children who could not be clearly classified, MRI demonstrated cerebral cortical atrophy and 18F-FDG PET exhibited multifocal glucose hypometabolism. Overall, this study demonstrated that the degree of brain metabolic abnormality was consistent with clinical seizure severity. In addition, 18F-FDG PET imaging after treatment was consistent with clinical outcomes. These findings indicate that 18F-FDG PET can be used to assess the severity of brain injury and prognosis in children with epileptic encephalopathy.     

Serotonin modulation of cerebral glucose metabolism measured with positron emission tomography (PET) in human subjects

To develop a method to measure the dynamic response of the serotonin system in vivo, the effects of intravenously administered citalopram (the most selective of the serotonin reuptake inhibitors) on cerebral glucose metabolism were evaluated. Cerebral glucose metabolism was measured with positron emission tomography (PET) in 14 normal subjects scanned after administration of saline placebo and citalopram administered on 2 separate days. Citalopram administration resulted in a decrease in metabolism in the right anterior cingulate gyrus (BA 24/32), right superior (BA 9) and right middle frontal gyrus (BA 6), right parietal cortex (precuneus), right superior occipital gyrus, left thalamus, and right cerebellum. Increased metabolism was observed in the left superior temporal gyrus and left occipital cortex. Alterations in metabolism by acute citalopram administration involved the heteromodal association cortices that also show metabolic alterations in patients with geriatric depression and overlap with the regions affected by antidepressant treatment. Future studies will evaluate how the acute metabolic response to citalopram relates to the metabolic response after chronic treatment in patients with geriatric depression.     

Effects of trihexyphenidyl and L-dopa on brain muscarinic cholinergic receptor binding measured by positron emission tomography

Summary The effects of pharmacological intervention on brain muscarinic cholinergic receptor (mAChR) binding were assessed in seven patients with Parkinson's disease by positron emission tomography and carbon-11 labelled N-methyl-4-piperidyl benzilate ([¹¹C]NMPB). [¹¹C]NMPB was injected twice, approximately 2 hours apart, in each patient, to assess the effect of single doses of 4 mg of trihexyphenidyl (n=5) or 400 mg of L-dopa with 57 mg of benserazide (n=2) on the binding parameter of mAChRs (K₃). There was a mean 28% inhibition of K₃ values in the brain in the presence of trihexyphenidyl, which was assumed to reflect mAChR occupancy. No significant change in K₃ was observed in the presence of L-dopa. This study demonstrates the feasibility of measuring mAChR occupancy by an anticholinergic medication with PET.     

Kinetic modeling and long‐term test‐retest reproducibility of the mGluR5 PET tracer 18F‐FPEB in human brain

¹⁸F‐FPEB is a promising PET tracer for studying the metabotropic glutamate subtype 5 receptor (mGluR5) expression in neuropsychiatric disorders. To assess the potential of ¹⁸F‐FPEB for longitudinal mGluR5 evaluation in patient studies, we evaluated the long‐term test‐retest reproducibility using various kinetic models in the human brain. Nine healthy volunteers underwent consecutive scans separated by a 6‐month period. Dynamic PET was combined with arterial sampling and radiometabolite analysis. Total distribution volume (V_T) and nondisplaceable binding potential (BP_ND) were derived from a two‐tissue compartment model without constraints (2TCM) and with constraining the K₁/k₂ ratio to the value of either cerebellum (2TCM‐CBL) or pons (2TCM‐PONS). The effect of fitting different functions to the tracer parent fractions and reducing scan duration were assessed. Regional absolute test‐retest variability (aTRV), coefficient of repeatability (CR) and intraclass correlation coefficient (ICC) were computed. The 2TCM‐CBL showed best fits. The mean 6‐month aTRV of V_T ranged from 8 to 13% (CR < 25%) with ICC > 0.6 for all kinetic models. BP_ND from 2TCM‐CBL with a sigmoid fit for the parent fractions showed the best reproducibility, with aTRV ≤ 7% (CR < 16%) and ICC > 0.9 in most regions. Reducing the scan duration from 90 to 60 min did not affect reproducibility. These results demonstrate for the first time that ¹⁸F‐FPEB brain PET has good long‐term reproducibility, therefore validating its use to monitor mGluR5 expression in longitudinal clinical studies. We suggest a 2TCM‐CBL with fitting a sigmoid function to the parent fractions to be optimal for this tracer. Synapse, 2016. © 2016 Wiley Periodicals, Inc. Synapse 70:153–162, 2016. © 2016 Wiley Periodicals, Inc.     

Quantitative imaging of neuroinflammation in human white matter: A positron emission tomography study with translocator protein 18 kDa radioligand, [18F]‐FEPPA

The ability to quantify translocator protein 18 kDa (TSPO) in white matter (WM) is important to understand the role of neuroinflammation in neurological disorders with WM involvement. This article aims to extend the utility of TSPO imaging in WM using a second‐generation radioligand, [¹⁸F]‐FEPPA, and high‐resolution research tomograph (HRRT) positron emission tomography (PET) camera system. Four WM regions of interests (WM‐ROI), relevant to the study of aging and neuroinflammatory diseases, were examined. The corpus callosum, cingulum bundle, superior longitudinal fasciculus, and posterior limb of internal capsule were delineated automatically onto subject's T₁‐weighted magnetic resonance image using a diffusion tensor imaging‐based WM template. The TSPO polymorphism (rs6971) stratified individuals to three genetic groups: high‐affinity binders (HAB), mixed‐affinity binders (MAB), and low‐affinity binders. [¹⁸F]‐FEPPA PET scans were acquired on 32 healthy subjects and analyzed using a full kinetic compartment analysis. The two‐tissue compartment model showed moderate identifiability (coefficient of variation 15–19%) for [¹⁸F]‐FEPPA total volume distribution (V_T) in WM‐ROIs. Noise affects V_T variability, although its effect on bias was small (6%). In a worst‐case scenario, ≤6% of simulated data did not fit reliably. A simulation of increased TSPO density exposed minimal effect on variability and identifiability of [¹⁸F]‐FEPPA V_T in WM‐ROIs. We found no association between age and [¹⁸F]‐FEPPA V_T in WM‐ROIs. The V_T values were 15% higher in HAB than in MAB, although the difference was not statistically significant. This study provides evidence for the utility and limitations of [¹⁸F]‐FEPPA PET to measure TSPO expression in WM. Synapse 68:536–547, 2014 . © 2014 Wiley Periodicals, Inc.     

Striatal dopamine metabolism in living monkeys examined by positron emission tomography

Positron emission tomography, using the dopa analogue [18F]6-fluoro-L-dopa, has been used to depict the neostriatum in living monkeys. The amount of 18F that accumulated preferentially in the striatum could be augmented by a peripheral decarboxylase inhibitor. Striatal 18F could also be discharged with reserpine. This is the first time that the regional distribution of a neurotransmitter has been demonstrated in monkeys.     

Detection of unknown primary tumours in patients with cerebral metastases using whole-body 18F-flouorodeoxyglucose positron emission tomography

Identification of the unknown primary tumours in patients presenting with cerebral metastasis is a continued diagnostic challenge. Despite extensive and lengthy diagnostic work-up, the primary tumours will remain obscure in a significant proportion of the patients. The aim of this study was to evaluate the use of whole-body 18-F-fluorodeoxyglucose positron emission tomography (18FDG PET) scanning in this pursuit. Sixteen patients aged 34-74 years, with histologically confirmed metastatic brain tumours, were included in the study. Whole-body 18FDG PET identified pulmonary foci of probable primary tumours in all patients. Subsequent confirmation of tumour tissue was determined either by direct histological verification or indirectly by the observation of lesion appearance or lesion growth on structural imaging. This could only be obtained in eight of 16 patients, all defined as true positive. Of the remaining eight, a biopsy could not be sampled from seven patients, because of death or limited follow-up investigations, and one patient had pulmonary malignant melanoma metastases. Whole-body 18FDG PET scanning is a sensitive tool in the search for unknown primary tumours of patients with confirmed cerebral metastases allowing early and focused histological confirmation from suspicious lesions.     

Cerebral glucose metabolism on positron emission tomography of children

Establishing the normative range of age‐dependent fluorodeoxyglucose (FDG) uptake in the developing brain is necessary for understanding regional quantitative analysis of positron emission tomography (PET) brain images in children and also to provide functional information on brain development. We analyzed head sections of FDG PET/computed tomography (CT) images for 115 patients (5 months to 23 years) without central nervous system disease before treatment, as PET studies are not performed on healthy children owing to ethical considerations and the risk of radiation exposure. We investigated the changes in FDG uptake and established age‐associated normative ranges of cerebral FDG. Head sections of FDG PET/CT images were registered to a population‐based probabilistic atlas of human cortical structures. Gray matter of 56 brain structures was defined on normalized PET images according to the atlas. To avoid individual and experimental confounding factors, the relative standardized uptake value (SUV) over the cerebellum of each structure was calculated. Relative SUVs were analyzed by ANOVA and modeled using generalized estimating equalization analysis with false discovery rate control. Age and structure were significant factors affecting SUVs. Anatomic proximity had little effect on FDG uptake. Linear and quadratic developmental trajectories were observed on absolute and relative SUVs, respectively. An increase from posterior‐to‐anterior and superior‐to‐inferior pattern was observed in both absolute SUV increase rate and relative SUV peak age. The SUV of each structure was modeled with respect to age, and these models can serve as baselines for the quantitative analysis of cerebral FDG–PET images of children. Hum Brain Mapp 35:2297–2309, 2014. © 2013 Wiley Periodicals, Inc .     

Comparative analysis of regional brain blood flow and glucose metabolism in focal cerebrovascular disease measured by dynamic positron emission tomography of fluorine-18-labelled tracers

Summary Regional cerebral blood flow (rCBF) and glucose metabolism (rCMRglc) were measured in 44 patients with various kinds of focal vascular brain lesions, using multislice positron emission tomography (PET). Haemodynamic data were obtained by a recently developed, non-invasive clearance method utilizing (¹⁸F)-methyl fluoride as a diffusible, gaseous indicator. Shortly after completion of each flow study, rCMRglc was dynamically determined by standard procedures using 2(¹⁸F)-fluorodeoxyglucose. While blood flow and glucose consumption in the structurally damaged area were often uncoupled during the acute phase, metabolism-to-flow ratios were markedly less scattered at later stages of cerebrovascular disease. Individual maximum-likelihood cluster analysis of brain regions revealed remarkable similarity between deactivation patterns of rCBF and rCMRglc, with Tanimoto coefficients averaging 0.56. This similarity was inversely related to the residual rCMRglc of the lesion. These findings are in line with results obtained by PET of other tracers, suggesting that the pair of methods provides valuable and somewhat complementary information on brain function and mechanisms of cerebral vascular disease.     

帕金森病痴呆患者的神经心理测试与18氟-氟代脱氧葡萄糖正电子发射断层摄影术脑显像分析

目的 研究帕金森病痴呆(PDD)患者的神经心理学特点及18氟-氟代脱氧葡萄糖(18F-FDG)PET脑代谢显像的影像学特征.方法 (1)对12例PDND患者、12例PDD患者和12名健康对照者运用蒙特利尔认知评估量表(MoCA)进行检查.(2)静脉注射18F-FDG后行PET脑代谢显像,获得12例PDND患者和12例PDD患者的PET图像.结果 (1)PDD组的MoCA总成绩(分)低于PDND组,其中MoCA子项目中的视空间与执行功能(1.50±1.08与4.25 ±0.87,t=-1.891)、注意(3.67±1.37与6.00 ±0.00,t’=-2.199)、语言(1.83 ±0.94与2.67±0.49,t'=-2.745)、抽象(0.67 ±0.65与1.75±0.45,t=-4.732)、延迟回忆(0.25 ±0.45与3.00±1.28,t’=-7.021)和定向(4.25±1.71与6.00±0.00,t’=-3.545)成绩低于PDND组,差异均具有统计学意义(均P＜0.05).PDD组MoCA总成绩低于健康对照组,差异具有统计学意义(15.10 ±3.82与28.10±1.16,t'=-11.280,P＜0.05).(2)18 F-FDG PET脑代谢显像:PDND组的大脑半球脑代谢不对称性轻度减低,PDD组的大脑半球脑代谢不对称性重度减低.结论 PDD表现为多认知域受损,以视空间与执行功能、注意、语言、抽象、延迟回忆和定向障碍较为严重.18F-FDG PET脑代谢显像检测对PDD的诊断可能有一定的帮助.     

The sensitivity of 18-fluorodopa positron emission tomography and magnetic resonance imaging in Parkinson''s disease

Parkinson's disease (PD) as the most important movement disorder is characterized by a progressive loss of nigral dopamine neurons and a subsequent degeneration within several other transmitter systems. Functional brain imaging with positron emission tomography (PET) and the radiotracer 18-fluorodopa (FDOPA) is capable to quantify the deficiency of dopamine synthesis and storage within pre-synaptic striatal nerve terminals. Therefore, FDOPA-PET allows the diagnosis of PD in early disease stages and the differentiation of clinically unclear cases from other movement disorders, e.g. essential tremor. Additionally, FDOPA-PET imaging permits the follow-up of disease progression, the assessment of medical and surgical PD therapy strategies with possible neuroprotective properties and the detection of pre-clinical disease in subjects at risk for the disorder. The classical domain of morphological magnetic resonance imaging (MRI) is the differentiation of symptomatic Parkinsonism from PD. However, recent advances in MRI data acquisition and analysis techniques demonstrated MRI to be also a valuable tool for detection of nigral pathology in PD and for differentiation of neurodegenerative disorders with atypical Parkinsonism.     

Glucose metabolism and rate constants in Alzheimer''s disease examined with dynamic positron emission tomography scan

Glucose metabolic rate constants in patients with Alzheimer's disease were analyzed using dynamic positron emission tomography with [18-F] fluoro-2-deoxyglucose (FDG). The cerebral metabolic rate of glucose (CMRG) was calculated using obtained rate constants, as well as the autoradiographic method. The half-life and distribution volume of FDG between the blood and the brain tissue were also calculated from obtained metabolic rate constants. The most severely affected metabolic step was the phosphorylation of glucose in the parietotemporal regions. The distribution volume of FDG showed no remarkable deviation from normal controls, while the half-life of FDG was found to be longer in the parietal and temporal regions. The CMRG from rate constants and that from the autoradiographic method showed no remarkable differences.     

A proposed method for the determination of cerebral regional intermediary glucose metabolism in humans in vivo using specifically labeled 11C-glucose and positron emission transverse tomography (PETT). I. An animal model with 14C-glucose and rat brain autoradiography

Based upon data obtained with our arterio-venous technique for the determination of cerebral metabolism in humans in vivo we have proposed a method for the determination of cerebral regional intermediary glucose metabolism in humans in vivo using specifically labeled ¹¹C-glucose and positron emission transverse tomography (PETT). In it we would give the subject successive intravenous injections of [3,4-¹¹C] glucose, [2,5-¹¹C] glucose and [1-¹¹C] glucose. There would be a 30 min period of continuous PETT measurements following each injection and a 2 hr interval after the first and second injections. The data would be used with suitable equations and algorithms to estimate for each specific region of the subject's brain the dynamics of the Embden-Meyerhof-Parnas (EMP) and the tricarboxylic acid cycle (TCA) metabolic pathways and the incorporation of glucose carbons into lactate, and the extent of dilution of glucose carbons in traversing the TCA with their subsequent incorporation into other carbon pools of the brain (ie, glutamate, glutamine, GABA, alanine). Using ¹⁴C as a model for ¹¹C and autoradiographs made with rat brain slices, we have produced an animal model to demonstrate the feasibility of our proposed method. The resulting autoradiographs have provided evidence of the validity of the predictions made from our arterio-venous data. The model was employed to show the selective reductions in the rates of incorporation of specific carbon atoms of glucose into regions of the rat brain and evidence of altered metabolic pathways following a single electroconvulsive shock (ECS) and after a series of nine ECS.     

Effect of gender on glucose utilization rates in healthy humans: a positron emission tomography study

Positron emission tomography (PET) was used with 18fluorodeoxyglucose to see if gender differences in resting cerebral glucose utilization could be detected. Thirty-two healthy subjects (15 women and 17 men; age range: 21-38 yr) were examined using a high-resolution PET scanner to determine the regional cerebral metabolic rate for glucose (CMRglc) in 65 gray matter regions of interest. Whole brain CMRglc did not differ significantly between the two genders, nor did any of the regional CMRglc values. Only 1 of 65 ratios of regional-to-whole brain CMRglc differed significantly between men and women, which is consistent with chance. These results indicate that there are no differences in resting regional cerebral glucose utilization between young men and women.