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Background: The Centiloid method has been proposed to enhance the comparability of amyloid PET quantification across different amyloid tracers and to provide a reference metric. In this study, we first quantified the impact of reconstruction parameters on Centiloid values for different reference regions, then we evaluated the reduction of this source of bias after PET image harmonization. Method: A total of 71 cognitively unimpaired participants from ALFA+ cohort were included in this study. For each participant a 18F‐flutemetamol PET scan and a T1‐weighted MRI scan were acquired. A Hoffman 3D‐brain phantom filled with 0.5 mCi of 18F‐FDG was scanned in the same tomograph. Participant and phantom PET data were reconstructed with 4 different protocols used in the clinical and research settings (Table1). The reconstruction with the coarsest spatial resolution was selected as the reference. The remaining 3 were harmonized to yield the same effective spatial resolution using the protocol used in the ADNI study. All images were quantified with a validated Centiloid pipeline using an AAL composite and different reference regions (Whole Cerebellum, Cerebellar Gray, Pons and White Matter). The mean absolute difference in Centiloids (CL) between different reconstructions of the same scan was calculated using the coarsest resolution as reference. Differences below 2.5 CL were considered to be irrelevant based on published test‐retest data. Result: Respectively, Figures 1 and 2 show the Hoffman phantom and the amyloid PET scans before and after harmonization. While mean absolute differences were below the test‐retest threshold for the Cerebellar Gray and whole cerebellum, differences up to 9 CL were observed for the Pons (Table2). White matter as reference region showed the biggest sensitivity to reconstruction parameters and the bias was dependent on the amyloid load (Figure 3c). After harmonization differences were always below the test‐retest threshold. Conclusion: Reconstruction parameters impact the Centiloid values as a function of reference region. While the impact using Cerebellar gray and the Whole Cerebellum was minor, important differences were observed when using the pons and white matter as reference regions. In all cases, harmonization of the effective spatial resolution was able to bring these biases below the test‐retest threshold. [ABSTRACT FROM AUTHOR]

Background: Several reports have described higher gray matter volumes and glucose consumption in cognitively unimpaired individuals with abnormal amyloid biomarkers, typically interpreted to be caused by inflammatory or compensatory mechanisms. In this study, we investigated structural and metabolic differences in cognitively unimpaired individuals with mismatching amyloid cerebrospinal fluid (CSF) and PET biomarkers (CSF+/PET‐), thought to be the earliest detectable Alzheimer's disease (AD) pathologic change. Additionally, we investigated whether inflammatory CSF biomarkers could explain such differences. Method: In 302 cognitively unimpaired participants of the ALFA study, we measured CSF Aβ42/40, phosphorylated tau (p‐tau), total tau (t‐tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100b and α‐synuclein using the exploratory Roche NeuroToolKit assays, a panel of robust prototype immunoassays (Roche Diagnostics International Ltd). Participants also underwent T1 MRI, [18F]flutemetamol amyloid PET, [18F]FDG PET and cognitive assessment (PACC). Amyloid PET was quantified with a validated pipeline to render Centiloid (CL) values. Individuals were classified into three groups: CSF‐/PET‐, CSF+/PET‐ and CSF+/PET+ using previously determined thresholds for positivity (Aβ42/40<0.071 and CL>30). Between‐group differences in Gray Matter volume (GMv) and [18F]FDG uptake were evaluated voxel‐wise with SPM12 (p<0.005, k>100) including age and sex as covariates. Additional models were implemented to measure possible mediation effects by inflammatory biomarkers (sTREM2, YKL40, GFAP, IL6, S100). Between‐group differences in cognition were also studied (p<0.05). Result: A total of 195 participants were CSF‐/PET‐, 82 were CSF+/PET‐ and 25 were CSF+/PET+ (Table 1). CSF+/PET‐ individuals displayed widespread higher GMv with respect to the reference CSF‐/PET‐ group as well as the CSF+/PET+ group (Fig. 1A). These differences were not mediated by inflammatory biomarkers. No significant between‐group differences were found in [18F]FDG uptake. PACC values were significantly higher in CSF+/PET‐ than the other groups (Fig. 1B) Conclusion: In cognitively unimpaired individuals, increases in GMv and cognitive functioning were observed in participants ]with abnormal amyloid CSF but PET negative. These increases could not be explained by measured neuroinflammatory CSF biomarkers. Even at the earliest stages of the AD continuum, factors enhancing resistance to amyloid plaque deposition might have a beneficial impact on cognition and could be used to inform prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Evidence shows that APOE‐ε4 is associated with amyloid‐beta (Aβ) aggregation in the medial temporal lobe (MTL), a crucial region supporting episodic memory (EM), early in the AD continuum. However, the impact of Aβ aggregation in the MTL of cognitively unimpaired (CU) APOE‐ε4 carriers has not been explored. We determine whether abnormal Aβ in the MTL of CU individuals APOE‐ε4 carriers has an impact on EM change. Method: The study included 352 CU ALFA+ study individuals (age 45‐70) who completed a baseline cognitive assessment with valid T1w MRI, [18F]‐flutemetamol Aβ PET, CSF, and APOE genotyping, and also had a second cognitive assessment after 3 years. [18F]‐flutemetamol scans were visually assessed globally to rate the scan as positive or negative and regionally. CSF p‐tau, Aβ‐40 and Aβ‐42 concentrations were determined using the exploratory Roche NeuroToolKit assays, a panel of automated robust prototype immunoassays, and Elecsys® immunoassays (both Roche Diagnostics International Ltd). Hippocampal volumes (HV) were obtained from the T1w MRIs with Freesurfer 6.0. EM was assessed by the Memory and Binding Tests subscore Total Paired Recall (TPR). Annualized memory change was the dependent variable in linear models using regional or global visual read (VR), CSF biomarkers and HV as predictors, and age, sex, education and APOE‐ε4 as covariates. Interaction terms with APOE‐ε4 *VR were also modeled. Result: 57 (16.2%) participants were global VR amyloid‐positive and 41 (71.9%) were APOE‐ε4 carriers. For annualized change in memory, we found that APOE‐ε4 carriership modified the association between temporal VR and annualized change (p=0.02) (Figure 1). 29 (5.4%) were amyloid‐positive in temporal VR, of them 19 (65.5%) APOE‐ε4 carriers. This interaction remained significant after adjusting by CSF Aβ42/Aβ40 and ptau/Aβ42 ratios, and HV (Table 1). No significant interaction was found with global VR. Conclusion: APOE‐ε4 carriers with a positive temporal VR exhibited a decline in EM. This result shows the effects on cognition of previous findings showing the association between APOE‐ε4 and Aβ aggregation in the MTL for any given level of soluble Aβ alterations. Moreover, this work supports that regional VRs can detect early Aβ pathology with relevant effects on cognition. [ABSTRACT FROM AUTHOR]

Introduction: [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is part of the regular preoperative work-up in medically refractory epilepsy. As a complement to visual evaluation of PET, statistical parametric maps can help in the detection of the epileptogenic zone (EZ). However, software packages currently available are time-consuming and little intuitive for physicians. We develop a user-friendly software (referred as PET-analysis) for EZ localization in PET studies that allows dynamic real-time statistical parametric analysis. To evaluate its performance, the outcome of PET-analysis was compared with the results obtained by visual assessment and Statistical Parametric Mapping (SPM). Methods: Thirty patients with medically refractory epilepsy who underwent presurgical 18F-FDG PET with good post-operative outcomes were included. The 18F-FDG PET studies were evaluated by visual assessment, with SPM8 and PET-analysis. In SPM, parametric T-maps were thresholded at corrected p < 0.05 and cluster size k = 50 and at uncorrected p < 0.001 and k = 100 (the most used parameters in the literature). Since PET-analysis rapidly processes different threshold combinations, T-maps were thresholded with multiple p -value and different clusters sizes. The presurgical EZ identified by visual assessment, SPM and PET-analysis was compared to the confirmed EZ according to post-surgical follow-up. Results: PET-analysis obtained 66.7% (20/30) of correctly localizing studies, comparable to the 70.0% (21/30) achieved by visual assessment and significantly higher (p < 0.05) than that obtained with the SPM threshold p < 0.001/k = 100, of 36.7% (11/30). Only one study was positive, albeit non-localizing, with the SPM threshold corrected p < 0.05/k = 50. Concordance was substantial for PET-analysis (κ = 0.643) and visual interpretation (κ = 0.622), being fair for SPM (κ = 0.242). Conclusion: Compared to SPM with the fixed standard parameters, PET-analysis may be superior in EZ localization with its easy and rapid processing of different threshold combinations. The results of this initial proof-of-concept study validate the clinical use of PET-analysis as a robust objective complementary tool to visual assessment for EZ localization. [ABSTRACT FROM AUTHOR]

Background: Weight loss is common in Alzheimer's disease (AD) and may start before cognitive impairment, but little is known about the relationship between weight change and AD biomarkers in the preclinical Alzheimer's continuum. We aimed to assess the association between weight change and AD biomarkers and cognitive performance in cognitively unimpaired (CU) adults from the ALFA+ study. Method: We analyzed data from 295 CU middle‐aged adults with two consecutive (mean interval 3.7 years) weight measures and neuropsychological assessments (n=267). Preclinical Alzheimer's Cognitive Composite (PACC) was computed as an average of z‐scores of episodic memory, semantic fluency and processing speed measures. We measured cerebrospinal fluid (CSF) levels of Aβ42, Aβ40, p‐tau, t‐tau, neurofilament light (NfL) and neurogranin using the Roche NeuroToolKit and Elecsys® immunoassays (n=280), and performed a [18F]flutemetamol PET scan in the follow‐up visit (n=252). PET results were dichotomized (Aβ positive or negative) based on visual read. Using established CSF cutoffs, we grouped participants in three biomarker categories: A‐T‐ (both Aβ and tau negative), A+T‐ (Aβ positive only) and A+T+ (both Aβ and tau positive). Linear and logistic regression and Kernel‐weighted local polynomial smoothing were used for analyses, which were adjusted by age, sex, body mass index, APOE genotype and years of education, as appropriate. Result: Weight loss predicted amyloid PET positivity (odds ratio 1.1, p=0.028) and was associated with significantly higher CSF levels of p‐tau (p=0.005), t‐tau (p=0.005) and neurogranin (p=0.002) (Table 1). Weight loss ≥5% (a standard cutoff for clinically relevant weight change) yielded 87% specificity and 30% sensitivity for amyloid PET positivity. Participants from the A+T+ group experienced significantly higher weight loss compared to A+T‐ (p=0.0029) and A‐T‐ (p=0.0005) groups (Figure 1). Weight loss was not associated with longitudinal changes in cognitive performance and preceded cognitive decline when using Aβ42/40 as a proxy of AD change progression (Table 1, Figure 2). Conclusion: Weight loss predicts amyloid PET positivity in CU middle‐aged adults. Our results suggest that weight loss is mainly related with changes in tau‐related and synaptic dysfunction biomarkers and may precede cognitive decline in the preclinical stage of the Alzheimer's continuum. [ABSTRACT FROM AUTHOR]

Background: Determining the presence of amyloid pathology in vivo is possible by visual read (VR) and quantification. VR is the method of reference for clinically assessing amyloid pathology, and guidelines are based on distinguishing positive scans from Alzheimer's dementia patients from healthy controls negative scans. More quantitative approaches using cut‐off values also focused on identification of early amyloid pathology in preclinical populations. This study investigated whether a VR‐defined cut‐off would perform similarly to recently proposed Centiloid (CL) cut‐offs. Methods: [18F]flutemetamol PET images of 352 cognitively unimpaired (CU) participants from the ALFA+ and 145 patients from the ADC cohort were included (Table 1). Scans were read by an experienced reader according to the product guidelines, collecting the number of positive regions (0‐5) and the final positive/negative classification. Tracer uptake was quantified with the standard CL pipeline. Using VR as the reference standard, previously proposed CL=12/30 cut‐offs were tested for sensitivity and specificity. In addition, a data‐driven cut‐off was determined using ROC analysis and the Youden Index. Results: 152 (30.6%) scans were read as positive. The CL=30 cut‐off resulted in 80.3% sensitivity and 100% specificity, while the CL=12 cut‐off greatly improved the sensitivity to 95.2% and kept a high specificity at 95.9%. Based on the ROC analysis, a CL=16 cut‐off was found, with both excellent sensitivity (93.9%) and specificity (98.2%) (AUC of.99, 95% CI:.989‐.998) (Figure 1). Mean CL values significantly increased with increasing number of visually positive regions (F=568.10, η2=.85, p<.01, Figure 2, Table 2). Number of visually positive regions was related to age in the ALFA+ CU population (F=9.17, η2=.12, p<.01). Conclusion: Using VR as reference standard, we found a similar CL cut‐off to that proposed by previous work using independent amyloid biomarkers (post‐mortem and CSF). These results illustrate that CL can be as sensitive as VR to early amyloid pathology. Importantly, these results could (at least partially) be attributed the level of experience of the reader and the inclusion of mainly cognitively unimpaired subjects. In addition, our results suggests that it can be of value to visually capture the extent of amyloid burden in addition to negative/positive classifications. [ABSTRACT FROM AUTHOR]

Background: CSF Aβ42 is thought to show AD‐related alterations earlier than amyloid‐β PET. Therefore, cognitively unimpaired (CU) individuals with abnormal CSF Aβ42 and normal amyloid‐β PET are believed to be in the earliest stages of the AD continuum. In this work, we sought to detect structural cerebral alterations in CU individuals with discordant status in these amyloid‐β biomarkers using Machine Learning techniques. Method: We included 498 CU individuals from the ALFA+ and ADNI studies with available MRI, amyloid‐β PET and CSF Aβ42 measurements, the latter measured with the exploratory Roche NeuroToolKit assays, a panel of automated robust prototype immunoassays. In addition, we calculated Centiloid (CL) values for the PET measurements. Individuals were categorized as CSF‐/PET‐, CSF+/PET‐ and CSF+/PET+ according to established cut‐offs (CSF Aβ42<1098pg/mL for ALFA+ and <880pg/mL for ADNI, and CL<17 for PET). We trained XGBoost classifiers to predict amyloid‐β positivity using as features age, sex, APOE‐ɛ4 status, brain volumes and cortical thicknesses, obtained with Freesurfer 6.0 and the Desikan‐Kiliany atlas. Relevant features for pairwise‐group classification were sought (CSF‐/PET‐ vs CSF+/PET‐; CSF+/PET‐ vs CSF+/PET+; CSF‐/PET‐ vs CSF+/PET+), calculating SHAP values to determine the most important features for prediction. Result: With respect the CSF‐/PET‐ group, the CSF+/PET‐ showed decreased gray matter volumes in the anterior and posterior cingulate/precuneus and increases in the lateral ventricles and bilateral parahippocampal gyri, among other regions (Figure 1A). Unexpectedly, the posterior cingulate/precuneus showed the opposite effect in cortical thickness measurements. These patterns were similar but more prominent in the comparison between the CSF‐/PET‐ vs CSF+/PET+ group (Figure 1B). Finally, CSF+/PET‐ group was characterized, with respect the CSF+/PET+ group by higher volume of the bilateral supramarginal gyri and lower cortical thickness in the posterior cingulate/precuneus (Figure 1C). Regarding the other variables in the model, APOE‐ɛ4 status was the most predictive variable in models with respect the CSF‐/PET‐ group and age in the CSF+/PET‐ vs CSF+/PET+ comparison. Conclusion: Our results show that model‐free machine learning techniques can detect complex brain morphological alterations in the earliest stages of the AD continuum. Interestingly, some regions showed increases in volume and/or cortical thickness which may reflect compensatory or inflammatory effects. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD) has been associated with increased risk of subsequent mild cognitive impairment (MCI) and dementia. Evidence from magnetic resonance imaging studies shows that neurodegenerative changes are already present years before dementia and thus, examining brain changes in SCD may contribute to identify potential biomarkers at an early stage of Alzheimer’s disease. Method: 198 individuals with SCD from the FACEHBI cohort were included (124 females; mean age 65.76 years). All subjects underwent magnetic resonance imaging and 18F‐Florbetaben positron emission tomography scan at baseline and were clinically follow‐up. Whole‐brain cortical surface‐based morphometry analysis were conducted using Freesurfer. Changes in cortical morphology (cortical thickness and surface area) were examined in relation to age, gender, brain amyloid beta deposition, ApoE‐e4 status (52 carrier/ 146 non carrier) and progression to MCI or dementia at the 4‐year follow‐up. Age, sex and years of education were included as covariates in all analyses. Result: At p=0.05 corrected, higher age was associated with widespread cortical thickness reduction and reduced surface area in bilateral parahippocampal, left cuneus and middle frontal and in the right superior frontal cortex. Males had reduced cortical thickness in the right lingual and reduced surface area in the right superior temporal cortex. Higher amyloid beta deposition was related to higher surface area in the left inferior parietal cortex and no significant results were found in relation to ApoE‐e4 status. At the 4‐year follow‐up, 33 subjects had progressed to MCI and 118 remained cognitively unimpaired, but there were no significant differences in baseline cortical thickness or surface area between them. With a liberal threshold of p<0.0001 uncorrected, we found a cluster of reduced cortical thickness in the right isthmus cingulate in those who converted to MCI four years later. Conclusion: Brain morphological changes in SCD are mainly characterized by cortical thickness reduction in relation to age and increased left inferior parietal surface area in relation to higher brain amyloid burden. Baseline reduced cortical thickness in the right isthmus cingulate is the only region associated with subsequent clinical progression to MCI and thus, it might be a useful predictive biomarker of cognitive decline in SCD individuals. [ABSTRACT FROM AUTHOR]

The 6-hydroxydopamine (6-OHDA) rodent model of Parkinson's disease (PD) has been used to evaluate the nigrostriatal pathway. The aim of this work was to explore the relationship between the degree of 6-OHDA-induced dopaminergic degeneration and [123I]FP-CIT binding using single photon emission computed tomography (SPECT). Fourteen rats received a 6-OHDA injection (4 or 8 µg) into the left medial forebrain bundle. After 3 weeks, magnetic resonance imaging and scans with a small-animal SPECT system were performed. Finally, the nigrostriatal lesion was assessed by immunohistochemical analysis. Immunohistochemical analysis confirmed two levels of dopaminergic degeneration. Lesions induced by 6-OHDA diminished the ipsilateral [123I]FP-CIT binding by 61 and 76%, respectively. The decrease in tracer uptake between control and lesioned animals was statistically significant, as was the difference between the two 6-OHDA lesioned groups. Results concluded that [123I]FP-CIT SPECT is a useful technique to discriminate the degree of dopaminergic degeneration in a rat model of PD. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Subjective Cognitive Decline (SCD) is a risk factor for cognitive decline and increases the likelihood of abnormal Alzheimer's disease (AD) biomarkers. A set of SCD features (SCDplus) has been proposed to be more strongly related with AD pathology, like onset within 5 years. Limited evidence suggest that there is an association between recent SCD onset and amyloid‐β (Aβ) levels but longitudinal studies exploring this association are lacking. Our objective was to explore the association between incidence and stability of SCD and biomarkers of AD pathology, synaptic dysfunction and neurodegeneration. Method: We analyzed clinical, neuroimaging and cerebrospinal fluid (CSF)‐biomarkers data from 261 cognitively unimpaired individuals from the ALFA+ study [mean age 57(5) at baseline]. SCD status was recorded at baseline and follow‐up [mean interval 48.5(8.6) months, 80% before 60 months] using the SCD‐Q question: Do you perceive memory or cognitive difficulties? Individuals were classified as Stable‐SCD [SCD at both visits (n=28)], Incident‐SCD [SCD only at follow‐up (n=44)], Unstable‐SCD [SCD only at baseline (n=21)], and non‐SCD [no SCD at any visit (n=168)]. All remained cognitively unimpaired at follow‐up. We defined amyloid status by visual reads (Aβ+/Aβ‐) from [18F]flutemetamol PET scans. Aβ40, Aβ42, p‐tau, t‐tau, neurogranin and Neurofilament Light (NfL) were measured with Roche NeuroToolKit and Elecsys® immunoassays (Roche Diagnostics). Logistic regression models were used to predict Aβ status and ANCOVA models to explore differences in biomarkers, adjusting for age, sex and interval between visits. Result: The proportion of Aβ+ individuals was higher in Incident‐SCD as compared to non‐SCD (OR=2.5, p=0.04, Table 1). Further, Incident‐SCD group displayed lower Aβ42/Aβ40 than non‐SCD (p=0.02, partial Eta2=0.02). While Stable‐SCD did not show differences in amyloid measures as compared to controls, NfL was significantly increased (p<0.0001, p‐Eta2=0.08) and t‐tau approached significance (p=0.08). Conclusion: Recent SCD onset was associated with amyloid‐β pathology, while stable SCD, even without clinical progression, was associated to biomarkers of neurodegeneration but not to amyloid pathology. These results support the usefulness of the onset in the last 5 years as SCDplus feature to detect amyloid pathology, while also highlights the role of neurodegeneration in SCD maintenance. [ABSTRACT FROM AUTHOR]

The aim of this work was to obtain a set of parameters to be applied in [123I]FP-CIT SPECT reconstruction in order to minimize the error between standardized and true values of the specific uptake ratio (SUR) in dopaminergic neurotransmission SPECT studies. To this end, Monte Carlo simulation was used to generate a database of 1380 projection data-sets from 23 subjects, including normal cases and a variety of pathologies. Studies were reconstructed using filtered back projection (FBP) with attenuation correction and ordered subset expectation maximization (OSEM) with correction for different degradations (attenuation, scatter and PSF). Reconstruction parameters to be optimized were the cut-off frequency of a 2D Butterworth pre-filter in FBP, and the number of iterations and the full width at Half maximum of a 3D Gaussian post-filter in OSEM. Reconstructed images were quantified using regions of interest (ROIs) derived from Magnetic Resonance scans and from the Automated Anatomical Labeling map. Results were standardized by applying a simple linear regression line obtained from the entire patient dataset. Our findings show that we can obtain a set of optimal parameters for each reconstruction strategy. The accuracy of the standardized SUR increases when the reconstruction method includes more corrections. The use of generic ROIs instead of subject-specific ROIs adds significant inaccuracies. Thus, after reconstruction with OSEM and correction for all degradations, subject-specific ROIs led to errors between standardized and true SUR values in the range [−0.5, +0.5] in 87% and 92% of the cases for caudate and putamen, respectively. These percentages dropped to 75% and 88% when the generic ROIs were used. [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate the influence of anatomical variability between subjects and of the partial volume effect (PVE) on the standardized Specific Uptake Ratio (SUR) in [123I]FP-bib SPECT studies. To this end, magnetic resonance (MR) images of 23 subjects with differences in the striatal volume of up to 44% were segmented and used to generate a database of 138 Monte Carlo simulated SPECT studies. Data included normal uptakes and pathological cases. Studies were reconstructed by filtered back projection (FBP) and the ordered-subset expectation-maximization algorithm. Quantification was carried out by applying a reference method based on regions of interest (ROIs) derived from the MR images and ROIs derived from the Automated Anatomical Labelling map. Our results showed that, regardless of anatomical variability, the relationship between calculated and true SUR values for caudate and putamen could be described by a multiple linear model which took into account the spill-over phenomenon caused by PVE ( for caudate and ≥0.980 for putamen) and also by a simple linear model (R2 ≥ 0.952 for caudate and ≥0.973 for putamen). Calculated values were standardized by inverting both linear systems. Differences between standardized and true values showed that, although the multiple linear model was the best approach in terms of variability ( ≥ 11.79 for caudate and  ≤7.36 for putamen), standardization based on a simple linear model was also suitable ( ≥ 12.44 for caudate and  ≤12.57 for putamen). [ABSTRACT FROM AUTHOR]

Purpose: We present a modified version of the SISCOM procedure that uses interictal PET instead of interictal SPECT for seizure onset zone localization. We called this new nuclear imaging processing technique PISCOM (PET interictal subtracted ictal SPECT coregistered with MRI).Methods: We retrospectively studied 23 patients (age range 4-61 years) with medically refractory epilepsy who had undergone MRI, ictal SPECT, interictal SPECT and interictal FDG PET and who had been seizure-free for at least 2 years after surgical treatment. FDG PET images were reprocessed (rFDG PET) to assimilate SPECT features for image subtraction. Interictal SPECT and rFDG PET were compared using statistical parametric mapping (SPM). PISCOM and SISCOM images were evaluated visually and using an automated volume of interest-based analysis. The results of the two studies were compared with each other and with the known surgical resection site.Results: SPM showed no significant differences in cortical activity between SPECT and rFDG PET images. PISCOM and SISCOM showed equivalent results in 17 of 23 patients (74%). The seizure onset zone was successfully identified in 19 patients (83%) by PISCOM and in 17 (74%) by SISCOM: in 15 patients (65%) the two techniques showed concordant successful results. The volume of interest-based analysis showed no significant differences between PISCOM and SISCOM in identifying the extension of the seizure onset zone. However, PISCOM showed a lower amount of indeterminate activity due to propagation, background or artefacts.Conclusion: Preliminary findings of this initial proof-of-concept study suggest that perfusion and glucose metabolism in the cerebral cortex can be correlated and that PISCOM may be a valid technique for identification of the seizure onset zone. However, further studies are needed to validate these results. [ABSTRACT FROM AUTHOR]