Hypometabolic Areas Research Articles

Single-Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma.

The effective treatment of advanced cervical cancer remains challenging. Herein, single‐nucleus RNA sequencing (snRNA‐seq) and SpaTial enhanced resolution omics‐sequencing (Stereo‐seq) are used to investigate the immunological microenvironment of cervical squamous cell carcinoma (CSCC). The expression levels of most immune suppressive genes in the tumor and inflammation areas of CSCC are not significantly higher than those in the non‐cancer samples, except for LGALS9 and IDO1. Stronger signals of CD56+ NK cells and immature dendritic cells are found in the hypermetabolic tumor areas, whereas more eosinophils, immature B cells, and Treg cells are found in the hypometabolic tumor areas. Moreover, a cluster of pro‐tumorigenic cancer‐associated myofibroblasts (myCAFs) are identified. The myCAFs may support the growth and metastasis of tumors by inhibiting lymphocyte infiltration and remodeling of the tumor extracellular matrix. Furthermore, these myCAFs are associated with poorer survival probability in patients with CSCC, predict resistance to immunotherapy, and might be present in a small fraction (< 30%) of patients with advanced cancer. Immunohistochemistry and multiplex immunofluorescence staining are conducted to validate the spatial distribution and potential function of myCAFs. Collectively, these findings enhance the understanding of the immunological microenvironment of CSCC and shed light on the treatment of advanced CSCC.

Cognitive decline and brainstem hypometabolism in long COVID: A case series.

ObjectiveTo assess FDG cerebral PET in patients suffering from cognitive impairment linked to Long COVID. The COVID pandemic has affected dozens of millions of people around the world and has resulted in the deaths of more than 3 million people. Following the acute forms, it has been reported sometimes long forms of COVID, with involvements of several organs including the brain. Neurological complications can include cognitive disturbances (brain fog) that are very common and can seriously disturb the life of patients.MethodsFluorodeoxyglucose PETs were performed in 3 patients with cognitive decline following COVID infection.ResultsWe report here 3 cases of brain fog with major hypometabolic areas of the pons revealed by the cerebral FDG PET.ConclusionThe dysfunction of the locus coeruleus in these patients could partly explain the cognitive disorders observed. Further studies involving larger cohorts of patients suffering from cognitive dysfunction will be needed to determine if the brainstem is frequently affected in these patients.

Molecular Imaging Findings on Acute and Long-Term Effects of COVID-19 on the Brain: A Systematic Review.

Molecular imaging techniques such as PET and SPECT have been used to shed light on how coronavirus disease 2019 (COVID-19) affects the human brain. We provide a systematic review that summarizes the current literature according to 5 predominant topics. First, a few case reports have suggested reversible cortical and subcortical metabolic alterations in rare cases with concomitant para- or postinfectious encephalitis. Second, imaging findings in single patients with the first manifestations of parkinsonism in the context of COVID-19 resemble those in neurodegenerative parkinsonism (loss of nigrostriatal integrity), but scarceness of data and a lack of follow-up preclude further etiologic conclusions (e.g., unmasking/hastening of neurodegeneration vs. infectious or parainfectious parkinsonism). Third, several case reports and a few systematic studies have addressed focal symptoms and lesions, most notably hyposmia. The results have been variable, although some studies found regional hypometabolism of regions related to olfaction (e.g., orbitofrontal and mesiotemporal). Fourth, a case series and systematic studies in inpatients with COVID-19–related encephalopathy (acute to subacute stage) consistently found a frontoparietal-dominant neocortical dysfunction (on imaging and clinically) that proved to be grossly reversible in most cases until 6 mo. Fifth, studies on post–COVID-19 syndrome have provided controversial results. In patients with a high level of self-reported complaints (e.g., fatigue, memory impairment, hyposmia, and dyspnea), some authors found extensive areas of limbic and subcortical hypometabolism, whereas others found no metabolic alterations on PET and only minor cognitive impairments (if any) on neuropsychologic assessment. Furthermore, we provide a critical appraisal of studies with regard to frequent methodologic issues and current pathophysiologic concepts. Finally, we devised possible applications of PET and SPECT in the clinical work-up of diagnostic questions related to COVID-19.

18F-FDG PET/CT and 99mTc-TRODAT Scan Findings in the Variants of Progressive Supranuclear Palsy and Correlation With Clinical Findings.

The aim of this study is to elucidate the patterns of characteristic hypometabolism on 18F-Fluoro Deoxy-glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) in the variants of Progressive supranuclear palsy (PSP) and its correlation with their core clinical features. A retrospective analysis of 88 subjects with clinically suspected PSP was done. An institutional informed consent to participate in the study was taken from all the subjects. All the subjects had undergone a prior 99mTechnetium labeled Tropane derivative of dopamine transporter Single Photon Emission Computed Tomography (99mTc TRODAT-1 SPECT) study and had abnormal scans to confirm degenerative parkinsonism. The subjects were clinically examined by the neurologists using the Progressive Supranuclear Palsy Rating Scale proposed by the Movement Disorder Society and were further clinically segregated into eight subtypes. All the included subjects further underwent a detailed clinical analysis to obtain their individual Schwab and England activities of daily living scale and Modified Hoehn and Yahr staging by a neurologist. All the subjects underwent 18F-FDG PET/CT scan after adequate preparation. The scans were analyzed both qualitatively (visually) and quantitatively using Statistical Parametric Mapping. The frontal, limbic, and sensorimotor cortices represented the common areas of hypometabolism among all the subtypes of PSP. The subcortical regions showing the most significant hypometabolism were the thalami, mid-brain, nucleus accumbens, caudate, globus pallidus, and putamen in descending order. Multiple cortical and subcortical regions of hypometabolism were identified in different subtypes of PSP. The characteristic patterns of hypometabolism observed in the different subgroups were more apparent on quantification and based on visual analysis alone, it may not be possible to differentiate the different subtypes of PSP. A good correlation was seen between some of the core clinical features and hypometabolic clusters.

The correspondence between morphometric MRI and metabolic profile in Rasmussen’s encephalitis

Volumetric magnetic resonance imaging (MRI) atrophy is a hallmark of Rasmussen’s encephalitis (RE). Here, we aim to investigate voxel-wise gray matter (GM) atrophy in RE, and its associations with glucose hypometabolism and neurotransmitter distribution utilizing MRI and PET data. In this study, fifteen RE patients and fourteen MRI normal subjects were included in this study. Voxel-wise GM volume and glucose metabolic uptake were evaluated using structural MRI and FDG-PET images, respectively. Spatial Spearman’s correlation was performed between GM atrophy of RE with FDG uptake alterations, and neurotransmitter distributions provided in the JuSpace toolbox. Compared with the control group, RE patients displayed extensive GM volume loss not only in the ipsilateral hemisphere, but also in the frontal lobe, basal ganglia, and cerebellum in the contralateral hemisphere. Within the RE group, the insular and temporal cortices exhibited significantly more GM atrophy on the ipsilesional than the contralesional side. FDG-PET data revealed significant hypometabolism in areas surrounding the insular cortices in the ipsilesional hemisphere. RE-related GM volumetric atrophy was spatially correlated with hypomebolism in FDG uptake, and with spatial distribution of the dopaminergic and serotonergic neurotransmitter systems. The spatial concordance of morphological changes with metabolic abnormalities suggest FDG-PET offers potential value for RE diagnosis. The GM alterations associated with neurotransmitter distribution map could provide novel insight in understanding the neuropathological mechanisms and clinical feature of RE.

Alzheimer's disease detection using explainable AI on PET images

AbstractBackgroundAutomated detection of Alzheimer’s disease features from imaging is a widely worked on machine learning problem, facilitated by the amount of data available through programs such as ADNI. Consequently, “black‐box” neural networks are starting to become viable and accurate approaches to patient classification. However, such methods are typically opaque, and their results are difficult to interpret – limiting their deployment in clinical trials.Our aim through this work is to apply recent advances in explainable deep neural networks and show that our model is indeed sensitive to the underlying metabolic processes. This makes the deep learning prediction process more transparent.MethodWe use 520 AC‐PC aligned [18F]‐FDG‐PET scans from the ADNI cohort from AD and healthy control (CG) groups. These are then fed to a deep neural network (ResNet, 3.4 million parameters), which learns to classify each scan. We then validate predictive capabilities of the model on 120 previously unseen scans.Using the validation data, we also calculate a saliency map for each scan. The map represents regions that were important for the model’s prediction. For each layer of the neural network, we calculate a cross‐entropy like quantity amongst the activations for a given layer. A group‐wise value is then calculated by averaging the subject maps within each group. The resulting difference highlights which voxels are activated during AD/CG classification. Principal component analysis reveals the regions of spatial location highest variance in the activations.ResultThe algorithm scored a mean accuracy of 89.2%. This is comparable with other approaches in the literature. Average saliency maps and their 2nd principal component can be seen in figures 1, 2 and 3.ConclusionThe algorithm is shown to accurately distinguish between AD and CG. By using the tools outlined above, we probe how the model arrives at those conclusions. The directions of maximal variance in the saliency maps shows the importance of the precuneus and hippocampi (increased saliency magnitude). This is corroborated by the difference in the mean CG and AD maps. These regions are known areas of FDG hypometabolism – a result previously identified and available in the literature.

Clinicoanatomical substrates of selfish behaviour in amyotrophic lateral sclerosis – An observational cohort study

ObjectiveALS primarily affects motor functions, but cognitive functions, including social understanding, may also be impaired. Von Economo neurons (VENs) are part of the neuronal substrate of social understanding and these cells are histopathologically altered in ALS. We investigated whether activity in areas including VENs is associated with an impairment of cognitive tasks that mirror social functioning. MethodsIn this observational prospective study, ALS patients (N = 26) were tested for cognitive behavioural function, encompassing different aspects of empathetic understanding (interpersonal reactivity index, IRI), social behaviour (ultimatum game), recognition of faux-pas situations, and general cognitive functioning (Edinburgh Cognitive and Behavioural ALS Screen, ECAS). For in vivo pathological staging according to Braak, DTI-MRI was performed to determine those ALS patients with expected pathological involvement of VENs (B ALS stages 3 + 4) compared to those without (B ALS stages 1 + 2). Expected hypometabolism of cerebral areas was determined with 18F-FDG PET in N = 20 ALS patients and compared to N = 20 matched healthy controls. Volume of interest analysis was performed in the anterior cingulate cortex (ACC) and the anterior insular cortex (AIC), which contain high numbers of VENs. ResultsCompared to those without expected pathological involvement of VENs (B/B ALS stages 1 + 2), ALS patients with anticipated pathological involvement of VENs (B/B ALS stages 3 + 4) presented with significantly reduced fantasy to understand the mindset of others (IRI) and, social behaviour was more selfish (ultimatum game) despite the fact that cognitive understanding of socially inappropriate behaviour of others (faux-pas) was unimpaired. 18F-FDG-PET showed hypometabolism in ACC and AIC in ALS patients with anticipated pathological involvement of VENs compared to those without and this was significantly correlated to cognitive-behavioral functions in certain tasks. ConclusionHere, we present evidence of altered social behaviour in ALS patients associated with regional 18FDG-PET hypometabolism in areas with a high density of VENs, thereby suggesting a possible causal association.

Presenilin-1 Mutations Are a Cause of Primary Lateral Sclerosis-Like Syndrome.

Background and PurposePrimary lateral sclerosis (PLS) is a progressive upper motor neuron (UMN) disorder. It is debated whether PLS is part of the amyotrophic lateral sclerosis (ALS) spectrum, or a syndrome encompassing different neurodegenerative diseases. Recently, new diagnostic criteria for PLS have been proposed. We describe four patients of two pedigrees, meeting definite PLS criteria and harboring two different mutations in presenilin 1 (PSEN1).MethodsPatients underwent neurological and neuropsychological examination, MRI, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), amyloid-related biomarkers, and next-generation sequencing (NGS) testing.ResultsFour patients, aged 25–45 years old, presented with a progressive UMN syndrome meeting clinical criteria of definite PLS. Cognitive symptoms and signs were mild or absent during the first year of the disease but appeared or progressed later in the disease course. Brain MRI showed microbleeds in two siblings, but iron-related hypointensities in the motor cortex were absent. Brain FDG-PET showed variable areas of hypometabolism, including the motor cortex and frontotemporal lobes. Amyloid deposition was confirmed with either cerebrospinal fluid (CSF) or imaging biomarkers. Two heterozygous likely pathogenic mutations in PSEN1 (p.Pro88Leu and p.Leu166Pro) were found in the NGS testing.ConclusionClinically defined PLS is a syndrome encompassing different neurodegenerative diseases. The NGS testing should be part of the diagnostic workup in patients with PLS, at least in those with red flags, such as early-onset, cognitive impairment, and/or family history of neurodegenerative diseases.

123I-Ioflupane SPECT and 18F-FDG PET Combined Use in the Characterization of Movement and Cognitive Associated Disorders in Neurodegenerative Diseases.

Both movement (MD) and cognitive (CD) disorders can occur associated in some neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). We further investigated the usefulness of 123I-Ioflupane SPECT and 18F-FDG PET combined use in patients with these disorders in the early stage. We retrospectively enrolled twenty-five consecutive patients with MD and CD clinical symptoms of recent appearance. All patients had undergone neurologic examination, neuropsychological tests, and magnetic resonance imaging. 123I-Ioflupane SPECT was performed in all cases, followed by 18F-FDG PET two weeks later. In the two procedures, both qualitative (QL) and quantitative (QN) image analyses were determined. In patients with both 123I-Ioflupane SPECT and 18F-FDG PET pathologic data, associated dopaminergic and cognitive impairments were confirmed in 56% of cases. Pathologic SPECT with normal PET in 16% of cases could diagnose MD and exclude an associated CD, despite clinical symptoms. On the contrary, normal SPECT with pathologic PET in 28% of cases could exclude basal ganglia damage while confirming CD. QN 123I-Ioflupane SPECT analysis showed better performance than QL since QN correctly characterized two cases of MD with normal QL. Moreover, correct classification of normal metabolism was made only by QN analysis of 18F-FDG PET in four cases, despite suspect areas of hypometabolism at QL. The combined use of these imaging procedures proved a reliable diagnostic tool to accurately identify and characterize MD and CD in early stage. QN analysis was effective in supporting QL evaluation, and its routine use is suggested, especially with inconclusive QL.

Effect of Point Spread Function Deconvolution in Reconstruction of Brain 18F-FDG PET Images on the Diagnostic Thinking Efficacy in Alzheimer's Disease.

Purpose: This study aims to determine the effect of applying Point Spread Function (PSF) deconvolution, which is known to improve contrast and spatial resolution in brain 18F-FDG PET images, to the diagnostic thinking efficacy in Alzheimer's disease (AD).Methods: We compared Hoffman 3-D brain phantom images reconstructed with or without PSF. The effect of PSF deconvolution on AD diagnostic clinical performance was determined from digital brain 18F-FDG PET images of AD (n = 38) and healthy (n = 35) subjects compared to controls (n = 36). Performances were assessed with SPM at the group level (p < 0.001 for the voxel) and at the individual level by visual interpretation of SPM T-maps (p < 0.005 for the voxel) by the consensual analysis of three experienced raters.Results: A mix of large hypometabolic (1,483cm3, mean value of −867 ± 492 Bq/ml) and intense hypermetabolic (902 cm3, mean value of 1,623 ± 1,242 Bq/ml) areas was observed in the PSF compared to the no PSF phantom images. Significant hypometabolic areas were observed in the AD group compared to the controls, for reconstructions with and without PSF (respectively 23.7 and 26.2 cm3), whereas no significant hypometabolic areas were observed when comparing the group of healthy subjects to the control group. At the individual level, no significant differences in diagnostic performances for discriminating AD were observed visually (sensitivity of 89 and 92% for reconstructions with and without PSF respectively, similar specificity of 74%).Conclusion: Diagnostic thinking efficacy performances for diagnosing AD are similar for 18F-FDG PET images reconstructed with or without PSF.

FDG-PET patterns associated with ideomotor apraxia and imitation apraxia in patients with corticobasal syndrome

IntroductionApraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. MethodsWe compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. ResultsIn patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. ConclusionGroup comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.

Long COVID hallmarks on [18F]FDG-PET/CT: a case-control study.

PurposeThe present study hypothesised that whole-body [18F]FDG-PET/CT might provide insight into the pathophysiology of long COVID.MethodsWe prospectively enrolled 13 adult long COVID patients who complained for at least one persistent symptom for >30 days after infection recovery. A group of 26 melanoma patients with negative PET/CT matched for sex/age was used as controls (2:1 control to case ratio). Qualitative and semi-quantitative analysis of whole-body images was performed. Fisher exact and Mann-Whitney tests were applied to test differences between the two groups. Voxel-based analysis was performed to compare brain metabolism in cases and controls. Cases were further grouped according to prevalent symptoms and analysed accordingly.ResultsIn 4/13 long COVID patients, CT images showed lung abnormalities presenting mild [18F]FDG uptake. Many healthy organs/parenchyma SUVs and SUV ratios significantly differed between the two groups (p ≤ 0.05). Long COVID patients exhibited brain hypometabolism in the right parahippocampal gyrus and thalamus (uncorrected p < 0.001 at voxel level). Specific area(s) of hypometabolism characterised patients with persistent anosmia/ageusia, fatigue, and vascular uptake (uncorrected p < 0.005 at voxel level).Conclusion[18F]FDG PET/CT acknowledged the multi-organ nature of long COVID, supporting the hypothesis of underlying systemic inflammation. Whole-body images showed increased [18F]FDG uptake in several “target” and “non-target” tissues. We found a typical pattern of brain hypometabolism associated with persistent complaints at the PET time, suggesting a different temporal sequence for brain and whole-body inflammatory changes. This evidence underlined the potential value of whole-body [18F]FDG PET in disclosing the pathophysiology of long COVID.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00259-021-05294-3.

18 F-FDG-PET hypometabolic pattern reveals multifocal epileptic foci despite limited unique stereotyped seizures

PurposeInterictal positron emission tomography (PET) with 18F-FDG has largely proved its utility in presurgical evaluation of drug-resistant epilepsies (DRE) and in the surgical outcomes. Interictal hypometabolism topography is related to the neuronal networks involved in the seizure onset zone (SOZ) and spread pathways. 18F-FDG PET has a good prognostic value for post-surgical outcome, especially in cases with unique focal ictal semiology and a limited extent of hypometabolism. Surprisingly few patients have similar limited ictal features but extended hypometabolism. The objective of this study is to show that stereoelectro encephalography (SEEG) provides an explanation for this large hypometabolism, which impacts the surgical strategy. MethodsA cohort of 248 patients underwent 18F-FDG PET and SEEG to explore for refractory epilepsy in two close tertiary epilepsy centers between January 2009 and December 2017. From this cohort, a subset of patients was selected with extended PET metabolism despite showing unique and limited ictal features in scalp EEG. The surgical outcome of this subset of patients has been analysed with respect to their FDG-PET and SEEG to understand the relationship between PET/SEEG/ presentation and surgical outcome. ResultsWe report a series of seven patients with DRE and unique stereotyped ictal semiology but extensive 18F-FDG-PET hypometabolism revealing unexpected multifocal SOZ using SEEG. All SOZ were encompassed by the hypometabolic area. ConclusionOur results demonstrate the necessity of accounting for the discrepancy between limited symptoms and widespread hypometabolism which can reveal multifocal SOZ. In those patients, surgical possibilities should be considered carefully.

Comprehensive Functional Evaluation of the Spectrum of Multi-System Atrophy with 18F-FDG PET/CT and 99mTc TRODAT-1 SPECT: 5 Year's Experience from a Tertiary Care Center.

Aim:To elucidate the patterns of characteristic hypometabolism on 18F- fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in multisystem atrophy (MSA) and their correlation with the patterns of uptake on dopamine transporter imaging with 99mTc TRODAT-1 SPECT.Material and Methods:A retrospective analysis of 67 patients with clinically diagnosed MSA was performed. All the subjects underwent 99mTc TRODAT-1 SPECT and 18F-FDG PET/CT scanning on two separate days. The 99mTc-TRODAT-1 scans were analyzed visually for asymmetry and rostro-caudal gradient. The FDG uptake patterns were recorded, and areas of hypometabolism that were two standard deviations from the mean were considered abnormal.Results:All the subjects had an abnormal pattern of FDG uptake on PET scan, both on a visual inspection and semiquantitative analysis. In MSA-P subjects (n = 29), diffuse predominant hypometabolism of the globus pallidus-putamen complex was noted, with relative sparing of the caudate nuclei. In MSA-C subjects (n = 25), characteristic hypometabolism was noted in the cerebellum and brainstem. In mixed subtypes (n = 13), variable involvement of the basal ganglia, cerebellum, and brainstem was noted with frontoparietal hypometabolism. A statistically significant difference between MSA-P and MSA-C for gradient reduction and asymmetry with gradient reduction was observed.Conclusion:Dopamine transporter imaging with 99mTc TRODAT-1 SPECT not only helps in confirmation of parkinsonian disorders but also demonstrates varying patterns of distribution in different subtypes of MSA. Characteristic patterns of hypometabolism in 18F-FDG PET may help in the differentiation of the subtypes of MSA in the presence of clinically overlapping symptoms.

A case report of a patient with mild cognitive impairment preceded by transient global amnesia with hypometabolism on FDG‐PET

AbstractBackgroundThis is the case of a 61‐year‐old Filipino female who presented with two episodes of transient global amnesia at the ages of 56 and 57.MethodThe patient underwent serial cranial MRI, cranial FDG‐PET/CT scan, and cognitive assessments over a period of five years.ResultCranial MRI at the time of the first episode in 2014 showed foci of restricted diffusion abnormality in the left hippocampus. Baseline cognitive assessment was negative for any impairment. On recurrence of TGA in 2015, brain FDG‐PET/CT scan was done which showed mild hypometabolism in the temporal and parietal cortices and hypometabolism in the posterior cingulate cortex. A second comprehensive cognitive assessment was negative for any impairment. Three years after the first episode (2017), she developed subtle changes in memory and thinking and had mild impairment in categorical fluency on neuropsychologic examination. Follow‐up cranial MRI (2017) showed slight decrease in hippocampal volumetry from the 43rd percentile to the 41st normative percentile. Follow‐up cranial FDG‐PET (2019) showed small mildly hypometabolic areas in the frontal, parietal and temporal lobes. The clinical assessment for the patient at this time is very mild cognitive impairment, non‐amnestic, probably secondary to a neurodegenerative process.ConclusionThis case study shows that transient global amnesia can recur and it may be a risk for cognitive impairment. It also illustrates that existing brain pathology related to a neurodegenerative process can be evident on neuroimaging despite very subtle clinical and neuropsychological cognitive changes. These findings also support aggressive preventive measures of delaying cognitive impairment.

Clinical impact of digital and conventional PET control databases for semi-quantitative analysis of brain 18F-FDG digital PET scans

PurposeDigital PET cameras markedly improve sensitivity and spatial resolution of brain 18F-FDG PET images compared to conventional cameras. Our study aimed to assess whether specific control databases are required to improve the diagnostic performance of these recent advances.MethodsWe retrospectively selected two groups of subjects, twenty-seven Alzheimer's Disease (AD) patients and twenty-two healthy control (HC) subjects. All subjects underwent a brain 18F-FDG PET on a digital camera (Vereos, Philips®). These two group (AD and HC) are compared, using a Semi-Quantitative Analysis (SQA), to two age and sex matched controls acquired with a digital PET/CT (Vereos, Philips®) or a conventional PET/CT (Biograph 6, Siemens®) camera, at group and individual levels. Moreover, individual visual interpretation of SPM T-maps was provided for the positive diagnosis of AD by 3 experienced raters.ResultsAt group level, SQA using digital controls detected more marked hypometabolic areas in AD (+ 116 cm3 at p < 0.001 uncorrected for the voxel, corrected for the cluster) than SQA using conventional controls. At the individual level, the accuracy of SQA for discriminating AD using digital controls was higher than SQA using conventional controls (86% vs. 80%, p < 0.01, at p < 0.005 uncorrected for the voxel, corrected for the cluster), with higher sensitivity (89% vs. 78%) and similar specificity (82% vs. 82%). These results were confirmed by visual analysis (accuracies of 84% and 82% for digital and conventional controls respectively, p = 0.01).ConclusionThere is an urgent need to establish specific digital PET control databases for SQA of brain 18F-FDG PET images as such databases improve the accuracy of AD diagnosis.

Direct comparison of brain [18F]FDG images acquired by SiPM-based and PMT-based PET/CT: phantom and clinical studies

BackgroundSilicon photomultiplier-positron emission tomography (SiPM-PET) has better sensitivity, spatial resolution, and timing resolution than photomultiplier tube (PMT)-PET. The present study aimed to clarify the advantages of SiPM-PET in 18F-fluoro-2-deoxy-D-glucose ([18F]FDG) brain imaging in a head-to-head comparison with PMT-PET in phantom and clinical studies.MethodsContrast was calculated from images acquired from a Hoffman 3D brain phantom, and image noise and uniformity were calculated from images acquired from a pool phantom using SiPM- and PMT-PET. Sequential PMT-PET and SiPM-PET [18F]FDG images were acquired over a period of 10 min from 22 controls and 10 patients. All images were separately normalized to a standard [18F]FDG PET template, then the mean standardized uptake values (SUVmean) and Z-score were calculated using MIMneuro and CortexID Suite, respectively.ResultsImage contrast, image noise, and uniformity in SiPM-PET changed 19.2, 3.5, and − 40.0% from PMT-PET, respectively. These physical indices of both PET scanners satisfied the criteria for acceptable image quality published by the Japanese Society of Nuclear Medicine of contrast > 55%, CV ≤ 15%, and SD ≤ 0.0249, respectively. Contrast was 70.0% for SiPM-PET without TOF and 59.5% for PMT-PET without TOF. The TOF improved contrast by 3.5% in SiPM-PET. The SUVmean using SiPM-PET was significantly higher than PMT-PET and did not correlate with a time delay. Z-scores were also significantly higher in images acquired from SiPM-PET (except for the bilateral posterior cingulate) than PMT-PET because the peak signal that was extracted by the calculation of Z-score in CortexID Suite was increased. The hypometabolic area in statistical maps was reduced and localized using SiPM-PET. The trend was independent of whether the images were derived from controls or patients.ConclusionsThe improved spatial resolution and sensitivity of SiPM-PET contributed to better image contrast and uniformity in brain [18F]FDG images. The SiPM-PET offers better quality and more accurate quantitation of brain PET images. The SUVmean and Z-scores were higher in SiPM-PET than PMT-PET due to improved PVE. [18F]FDG images acquired using SiPM-PET will help to improve diagnostic outcomes based on statistical image analysis because SiPM-PET would localize the distribution of glucose metabolism on Z-score maps.

Utility of hybrid PET/MRI multiparametric imaging in navigating SEEG placement in refractory epilepsy

PurposeStereo-electroencephalography (SEEG) implantation before epilepsy surgery is critical for precise localization and complete resection of the seizure onset zone (SOZ). Combined metabolic and morphological imaging using hybrid PET/MRI may provide supportive information for the optimization of the SEEG coverage of brain structures. In this study, we originally imported PET/MRI images into the SEEG positioning system to evaluate the application of PET/MRI in guiding SEEG implantation in refractory epilepsy patients. MaterialsForty-two patients undergoing simultaneous PET/MRI examinations were recruited. All the patients underwent SEEG implantation guided by hybrid PET/MRI and surgical resection or ablation of epileptic lesion. Surgery outcome was assessed using a modified Engel classification one year (13.60 ± 2.49 months) after surgery. Areas of SOZ were identified using hybrid PET/MRI and concordance with SEEG was evaluated. Logistic regression analysis was used to predict the presence of a favorable outcome with the coherence of concordance of PET/MRI and SEEG. ResultsHybrid PET/MRI (including visual PET, MRI, plus MI Neuro) identified SOZ lesions in 38 epilepsy patients (90.47 %). PET/MRI showed the same SOZ localization with SEEG in 29 patients (69.05 %), which was considered to be concordant. The concordance between the PET/MRI and SEEG findings was significantly predictive of a successful surgery outcome (odds ratio = 20.41; 95 % CI = 2.75–151.4, P = 0.003**). ConclusionHybrid PET/MRI combined visual PET, multiple sequences MRI and SPM PET helps identify epilepsy lesions particularly in subtle hypometabolic areas. Patients with concordant epileptic lesion localization on PET/MRI and SEEG demonstrated a more favorable outcome than those with inconsistent localization between modalities.

Focal cortical dysplasia imaging discrepancies between MRI and FDG-PET: Unique association with temporal lobe location

PurposeAlthough magnetic resonance imaging (MRI) and 18F-2-fluorodeoxyglucose-positron emission tomography (FDG-PET) are used for pre-surgical assessment of focal cortical dysplasia (FCD), they often disagree. This study aimed to identify factors that contribute to discrepancies in FCD imaging between MRI and FDG-PET. MethodsSixty-two patients (mean age, 18.9 years) with a FCD type I or II were retrospectively selected. These patients were visually categorized into two groups: 1) extent of PET abnormality larger than MRI abnormality and 2) vice versa or equivalent. Predictive factors of these two groups were analyzed by multivariate logistic regression. The extent of hypometabolic transient zone surrounding FCDs and their mean standardized uptake values were measured and compared by the Mann–Whitney U-test. ResultsFCDs were detected on MRI and PET in 46 and 55 patients, respectively, whereas no abnormality was detected in 4 patients. The PET hypometabolic areas were larger than the MRI abnormal areas in 26 patients (88 % in the temporal lobe), whereas the PET hypometabolic areas were equivalent or smaller than the MRI abnormal areas in 32 patients (69 % in the frontal lobe). The temporal lobe location was an independent predictor for differentiating the two groups (OR = 35.2, 95 % CI = 6.81–168.0, P < .001). The temporal lobe lesions had significantly wider transient zones and lower standardized uptake values than those in the other lobes (P < .001, both). ConclusionThe discrepancies between MRI and FDG-PET findings of FCD were associated with temporal lobe location.

Do cognitive reserve levels affect brain glucose metabolism and amyloid-β depositions in subjective cognitive decline subjects?

Subjective cognitive decline (SCD) is the preclinical stage of Alzheimer's disease (AD). Abnormal brain glucose metabolism and Aβ depositions can be observed in SCD subjects. Nevertheless, there was not cognitive impaired performance in standardized neuropsychological in these subjects. Cognitive reserve (CR) could be the reason to explain this phenomenon. However, correspondence between CR and SCD was still uncleared. In this study, we attained 74 subjects underwent 18FFDG PET scans (SCD1 group) and 38 patients underwent 18FAV45 PET scans (SCD2 group) from Xuanwu Hospital, Beijing, China. First, SCD1 group was divided into SCD1H (high CR, n=33, educational years>12) and SCD1L (low CR, n=41, educational years<=12) groups. The SCD2 group was divided into SCD2H (high CR, n=17, educational years>12) and SCD2L (low CR, n=21, educational years<=12) groups. Second, we calculated standardized uptake value rate (SUVR) values of 18FFDG PET and 18F-AV45 PET images in voxel-wise level. Third, the two-sample t-test between low and high CR groups was used to investigate the effects of CR. As a result, the SUVR values of FDG-PET images in SCD1H (0.89±0.11) were significant lower than SCD1L (0.96±0.13, p=0.017). The SUVR values of AV45PET images in SCD2H (0.63±0.11) were significant lower than SCD2L (0.78±0.15, p=0.001). In addition, the frontal lobe was found as the main area of hypometabolism and reduced AB depositions. As a conclusion, there are differential glucose metabolism and Aβ deposition patterns in SCD subjects between low and high CR groups.