Estudio de la estabilidad temporal de métricas electrofisiológicas en pacientes con fibrilación auricular

[ES] La ablación con catéter es uno de los principales tratamientos para la restauración del ritmo sinusal en pacientes con fibrilación auricular (FA). Sin embargo, la tasa de éxito de este tipo de terapias está lejos de la deseada. El objetivo de este trabajo es estudiar si la estabilidad temporal de métricas electrofisiológicas obtenidas de señales cardíacas puede ser usada como predictor de la recurrencia de la FA tras la ablación. Para este estudio se han obtenido parámetros de señales de electrogramas (EGMs), Body Surface Potential Mapping (BSPM) e imagen electrocardiográfica (ECGI) para 29 pacientes de FA. La estabilidad temporal de dichas métricas ha sido evaluada a corto plazo (intervalos de entre 8 y 12 s) y a largo plazo (>5 min), y ha sido comparada con el estado de cada paciente 12 meses tras la ablación. Los pacientes incapaces de mantener el ritmo sinusal 12 meses tras la ablación han demostrado una mayor variabilidad temporal a corto plazo en métricas basadas en frecuencias de activación de EGMs intracardiacos (p=0.045) y de ECGI (p=0.043), así como en métricas basadas en la actividad reentrante identificada a partir de EGMs intracardiacos (p=0.060) y de ECGI (p=0.079). Se han observado también diferencias significativas a largo plazo en métricas de frecuencias de activación de EGMs intracardiacos (p=0.028) y ECGI (p=0.017). Además, se ha observado que la introducción de parámetros de calidad de EGMs mejora la discriminación entre grupos de pacientes en métricas de frecuencias de activación a corto (p=0.033) y a largo plazo (p=0.010), y de reentradas eléctricas a corto plazo (p=0.045). La estabilidad temporal de métricas basadas en frecuencias de activación y en la identificación de actividad reentrante, obtenidas de forma invasiva y no invasiva, están asociadas a la recurrencia de la FA en pacientes derivados a terapias de ablación.[EN] Catheter ablation is one of the main therapies for restoring sinus rhythm in patients with atrial fibrillation (AF). However, AF termination ratios are far from satisfactory. The aim of this work is to study if the temporal stability of electrophysiological metrics can be used as a predictor of AF recurrence. For this study, signal parameters were obtained from electrograms (EGMs), Body Surface Potential Mapping (BSPM) and electrocardiographic imaging (ECGI) for 29 AF patients. Temporal stability of these parameters was evaluated for short-term (between 8 and 12 s) and long-term intervals (>5 min) and compared with the 12-month post-ablation follow-up for each patient. Patients unable to maintain sinus rhythm 12 months after ablation have shown a higher temporal variability for short-term intervals on metrics based on activation frequencies of intracardiac EGMs (p=0.045) and ECGI (p=0.043), as well as on metrics based on reentrant activity obtained from intracardiac EGMs (p=0.060) and ECGI (p=0.079). Significant differences were also found for long-term intervals on metrics based on activation frequencies of intracardiac EGMs (p=0.028) and ECGI (p=0.017). Moreover, inclusion of EGM quality parameter in the analysis has shown an improvement of the results both for metrics based on activation frequencies in the short- (p=0.033) and long-term (p=0.010) and for metrics based on reentrant activity in the short-term (p=0.045). Temporal stability of metrics based on activation frequencies and identification of reentrant activity, obtained both through invasive and non-invasive procedures, is associated with the AF recurrence on patients derived for catheter ablation.[CA] L’ablació amb catèter és un dels principals tractaments per restaurar el ritme sinusal en pacients amb fibril·lació auricular (FA). No obstant, la taxa d’èxit d’aquest tipus de teràpies és lluny de ser la desitjada. L’objectiu d’aquest treball és estudiar si, l’estabilitat temporal de mètriques electrofisiològiques obtingudes de senyals cardíaques, pot utilitzar-se com a predictor de la recurrència de la FA després de l’ablació. Per a aquest estudi s’han obtingut paràmetres de senyals d’electrogrames (EGMs), Body Surface Potential Mapping (BSPM) i imatge electrocardiogràfica (ECGI) per a 29 pacients de FA. L’estabilitat temporal d’aquestes mètriques s’ha avaluat a curt termini (intervals d’entre 8 i 12 s) i a llarg termini (>5min), i s’ha comparat amb l’estat de cada pacient, 12 mesos després de l’ablació. Els pacients que no han mantingut ritme sinusal 12 mesos després de l’ablació han demostrat una major variabilitat temporal a curt termini en mètriques basades en freqüències d’activació d’EGMs intracardíacs (p=0.045) i d’ECGI (p=0.043), així com en la variabilitat de l’activitat reentrant identificada a partir d’EGMs intracardíacs (p=0.060) i d’ECGI (p=0.079). S’hi han observat també diferències significatives a llarg termini en mètriques de freqüències d’activació d’EGMs intracardíacs (p=0.028) i d’ECGI (p=0.017). Així mateix, s’hi ha observat que la introducció de paràmetres de qualitat d’EGMs millora la discriminació entre grups de pacients en mètriques de freqüència d’activació a curt (p=0.033) i a llarg termini (p=0.010), i de reentrades elèctriques a curt termini (p=0.045). L’estabilitat temporal de mètriques basades en freqüències d’activació i en la identificació d’activitat reentrant, obtingudes de forma invasiva i no invasiva, estan associades a la recurrència de la FA en pacients derivats a teràpies d’ablació.Costoya Sánchez, A. (2019). Estudio de la estabilidad temporal de métricas electrofisiológicas en pacientes con fibrilación auricular. http://hdl.handle.net/10251/123099TFG

Non-invasive Spatial Mapping of Frequencies in Atrial Fibrillation: Correlation With Contact Mapping

Introduction: Regional differences in activation rates may contribute to the electrical substrates that maintain atrial fibrillation (AF), and estimating them non-invasively may help guide ablation or select anti-arrhythmic medications. We tested whether non-invasive assessment of regional AF rate accurately represents intracardiac recordings. Methods: In 47 patients with AF (27 persistent, age 63 ± 13 years) we performed 57-lead non-invasive Electrocardiographic Imaging (ECGI) in AF, simultaneously with 64-pole intracardiac signals of both atria. ECGI was reconstructed by Tikhonov regularization. We constructed personalized 3D AF rate distribution maps by Dominant Frequency (DF) analysis from intracardiac and non-invasive recordings. Results: Raw intracardiac and non-invasive DF differed substantially, by 0.54 Hz [0.13 - 1.37] across bi-atrial regions (R2 = 0.11). Filtering by high spectral organization reduced this difference to 0.10 Hz (cycle length difference of 1 - 11 ms) [0.03 - 0.42] for patient-level comparisons (R2 = 0.62), and 0.19 Hz [0.03 - 0.59] and 0.20 Hz [0.04 - 0.61] for median and highest DF, respectively. Non-invasive and highest DF predicted acute ablation success (p = 0.04). Conclusion: Non-invasive estimation of atrial activation rates is feasible and, when filtered by high spectral organization, provide a moderate estimate of intracardiac recording rates in AF. Non-invasive technology could be an effective tool to identify patients who may respond to AF ablation for personalized therapy

Increased Medial Temporal Tau Positron Emission Tomography Uptake in the Absence of Amyloid-β Positivity

IMPORTANCE: An increased tau positron emission tomography (PET) signal in the medial temporal lobe (MTL) has been observed in older individuals in the absence of amyloid-β (Aβ) pathology. Little is known about the longitudinal course of this condition, and its association with Alzheimer disease (AD) remains unclear. OBJECTIVE: To study the pathologic and clinical course of older individuals with PET-evidenced MTL tau deposition (TMTL+) in the absence of Aβ pathology (A-), and the association of this condition with the AD continuum. DESIGN, SETTING, AND PARTICIPANTS: A multicentric, observational, longitudinal cohort study was conducted using pooled data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), Harvard Aging Brain Study (HABS), and the AVID-A05 study, collected between July 2, 2015, and August 23, 2021. Participants in the ADNI, HABS, and AVID-A05 studies (N = 1093) with varying degrees of cognitive performance were deemed eligible if they had available tau PET, Aβ PET, and magnetic resonance imaging scans at baseline. Of these, 128 participants did not meet inclusion criteria based on Aβ PET and tau PET biomarker profiles (A+ TMTL-). EXPOSURES: Tau and Aβ PET, magnetic resonance imaging, cerebrospinal fluid biomarkers, and cognitive assessments. MAIN OUTCOMES AND MEASURES: Cross-sectional and longitudinal measures for tau and Aβ PET, cortical atrophy, cognitive scores, and core AD cerebrospinal fluid biomarkers (Aβ42/40 and tau phosphorylated at threonine 181 p-tau181 available in a subset). RESULTS: Among the 965 individuals included in the study, 503 were women (52.1%) and the mean (SD) age was 73.9 (8.1) years. A total of 51% of A- individuals and 78% of A+ participants had increased tau PET signal in the entorhinal cortex (TMTL+) compared with healthy younger (aged <39 years) controls. Compared with A- TMTL-, A- TMTL+ participants showed statistically significant, albeit moderate, longitudinal (mean [SD], 1.83 [0.84] years) tau PET increases that were largely limited to the temporal lobe, whereas those with A+ TMTL+ showed faster and more cortically widespread tau PET increases. In contrast to participants with A+ TMTL+, those with A- TMTL+ did not show any noticeable Aβ accumulation over follow-up (mean [SD], 2.36 [0.76] years). Complementary cerebrospinal fluid analysis confirmed longitudinal p-tau181 increases in A- TMTL+ in the absence of increased Aβ accumulation. Participants with A- TMTL+ had accelerated MTL atrophy, whereas those with A+ TMTL+ showed accelerated atrophy in widespread temporoparietal brain regions. Increased MTL tau PET uptake in A- individuals was associated with cognitive decline, but at a significantly slower rate compared with A+ TMTL+. CONCLUSIONS AND RELEVANCE: In this study, individuals with A- TMTL+ exhibited progressive tau accumulation and neurodegeneration, but these processes were comparably slow, remained largely restricted to the MTL, were associated with only subtle changes in global cognitive performance, and were not accompanied by detectable accumulation of Aβ biomarkers. These data suggest that individuals with A- TMTL+ are not on a pathologic trajectory toward AD

Temporal Stability of Dominant Frequency as Predictor of Atrial Fibrillation Recurrence

[EN] Catheter ablation is one of the main therapies for restoring sinus rhythm in patients with atrial fibrillation (AF), yet AF termination ratios are far from satisfactory. The goal of this work is to study if temporal stability of dominant frequencies (DFs) of electrograms (EGMs) can be used as predictor of AF recurrence. EGMs were recorded from 29 AF patients using 64- pole basket catheters during the ablation procedure. DFs before ablation were obtained for 4-second overlapping fragments of EGM recordings with a 0.4 s shift, and their temporal stability was evaluated for short-term (between 8 and 12 s) and long-term time intervals (>5 min). Patients were classified as AF (N=15) if sinus rhythm was not maintained in a 12-month post-ablation followup, and AF free otherwise (N=14). Significant differences were found in the short-term analysis between AF free and AF patients for the difference between the mode value in DFs (p=0.045), as well as for the long-term analysis for the normalized average between DFs (p=0.028) and the average between DFs (p=0.043). More stable values were found for AF free patients for all statistically significant metrics. Short- and long-term temporal stability of DF values of EGM signals were found to be associated with the 12- month success rate of ablative therapies of AF patients.This work was supported by the Instituto de Salud Carlos III FEDER (DTS16/00160; PI16/01123; PI17/01059; PI17/01106), the EIT-HEALTH 19600 AFFINE and the Valencian Regional Government (AICO2018).Costoya-Sánchez, A.; Climent, AM.; Hernández-Romero, I.; Liberos, A.; Fernández-Avilés, F.; Narayan, SM.; Atienza, F.... (2019). Temporal Stability of Dominant Frequency as Predictor of Atrial Fibrillation Recurrence. IEEE. 1-4. https://doi.org/10.22489/CinC.2019.360S1

Automatic Quality Electrogram Assessment Improves Reentrant Activity Identification in Atrial Fibrillation

[EN] Location of reentrant electrical activity responsible for driving atrial fibrillation (AF) is key to ablative therapies. The aim of this work is to study the effect of the quality of the electrograms (EGMs) used for 3D phase analysis on reentrant activity identification, as well as to develop an algorithm capable of automatically identifying lowquality signals. EGMs signals from 259 episodes obtained from 29 AF patients were recorded using 64-electrode basket catheters. Low-quality EGMs were manually identified. Reentrant activity was identified in 3D phase maps and provided an area under the ROC curve (AUC) of 0.69 when compared to a 2D activation-based method. Reentries located in regions with poor-quality EGMs were then removed, increasing the AUC to 0.80. The EGM classification algorithm showed a similar performance both for low-quality EGM identification (sensitivity 0.91 and specificity 0.80) and for reentrant activity location with 3D phase analysis (AUC 0.80). Discard of reentrant activity identified in regions where EGMs showed low quality significantly improved the specificity of the 3D phase analysis. Besides, EGMs classification according to their quality proved to be possible using time and spectral domain parameters.This work was supported by the Instituto de Salud Carlos III FEDER (DTS16/00160; PI16/01123; PI17/01059; PI17/01106), the EIT-Health 19600 AFFINE and the Valencian Regional Government (AICO2018).Costoya-Sánchez, A.; Climent, AM.; Hernández-Romero, I.; Liberos, A.; Fernández-Avilés, F.; Narayan, SM.; Atienza, F.... (2019). Automatic Quality Electrogram Assessment Improves Reentrant Activity Identification in Atrial Fibrillation. IEEE. 1-4. https://doi.org/10.22489/CinC.2019.349S1

Automatic quality electrogram assessment improves phase-based reentrant activity identification in atrial fibrillation

[EN] Identification of reentrant activity driving atrial fibrillation (AF) is increasingly important to ablative therapies. The goal of this work is to study how the automatically-classified quality of the electrograms (EGMs) affects reentrant AF driver localization. EGMs from 259 AF episodes obtained from 29 AF patients were recorded using 64-poles basket catheters and were manually classified according to their quality. An algorithm capable of identifying signal quality was developed using time and spectral domain parameters. Electrical reentries were identified in 3D phase maps using phase transform and were compared with those obtained with a 2D activation-based method. Effect of EGM quality was studied by discarding 3D phase reentries detected in regions with low-quality EGMs. Removal of reentries identified by 3D phase analysis in regions with low-quality EGMs improved its performance, increasing the area under the ROC curve (AUC) from 0.69 to 0.80. The EGMs quality classification algorithm showed an accurate performance for EGM classification (AUC 0.94) and reentry detection (AUC 0.80). Automatic classification of EGM quality based on time and spectral signal parameters is feasible and accurate, avoiding the manual labelling. Discard of reentries identified in regions with automatically-detected poor-quality EGMs improved the specificity of the 3D phase-based method for AF driver identification.Supported in part by: Instituto de Salud Carlos III FEDER (Fondo Europeo de Desarrollo Regional; IJCI-2014-22178, DTS16/00160; PI16/01123; PI17/01059; PI17/01106), Generalitat Valenciana Grants (APOSTD/2017 and APOSTD/2018) and projects (GVA/2018/103); National Institutes of Health (R01 HL85537; K24 HL103800); EIT-Health 19600 AFFINE; Nvidia Corporation (donation grants).Costoya-Sánchez, A.; Climent, AM.; Hernández-Romero, I.; Liberos Mascarell, A.; Fernández-Avilés, F.; Narayan, SM.; Atienza, F.... (2020). Automatic quality electrogram assessment improves phase-based reentrant activity identification in atrial fibrillation. Computers in Biology and Medicine. 117:1-8. https://doi.org/10.1016/j.compbiomed.2019.103593S18117Atienza, F., Almendral, J., Jalife, J., Zlochiver, S., Ploutz-Snyder, R., Torrecilla, E. G., … Berenfeld, O. (2009). Real-time dominant frequency mapping and ablation of dominant frequency sites in atrial fibrillation with left-to-right frequency gradients predicts long-term maintenance of sinus rhythm. Heart Rhythm, 6(1), 33-40. doi:10.1016/j.hrthm.2008.10.024Guillem, M. S., Climent, A. M., Rodrigo, M., Fernández-Avilés, F., Atienza, F., & Berenfeld, O. (2016). Presence and stability of rotors in atrial fibrillation: evidence and therapeutic implications. Cardiovascular Research, 109(4), 480-492. doi:10.1093/cvr/cvw011Haïssaguerre, M., Hocini, M., Sanders, P., Takahashi, Y., Rotter, M., Sacher, F., … Jaïs, P. (2006). Localized Sources Maintaining Atrial Fibrillation Organized by Prior Ablation. Circulation, 113(5), 616-625. doi:10.1161/circulationaha.105.546648Narayan, S. M., Krummen, D. E., Shivkumar, K., Clopton, P., Rappel, W.-J., & Miller, J. M. (2012). Treatment of Atrial Fibrillation by the Ablation of Localized Sources. Journal of the American College of Cardiology, 60(7), 628-636. doi:10.1016/j.jacc.2012.05.022Atienza, F., Almendral, J., Ormaetxe, J. M., Moya, Á., Martínez-Alday, J. D., Hernández-Madrid, A., … Jalife, J. (2014). Comparison of Radiofrequency Catheter Ablation of Drivers and Circumferential Pulmonary Vein Isolation in Atrial Fibrillation. Journal of the American College of Cardiology, 64(23), 2455-2467. doi:10.1016/j.jacc.2014.09.053Sanders, P., Berenfeld, O., Hocini, M., Jaïs, P., Vaidyanathan, R., Hsu, L.-F., … Haïssaguerre, M. (2005). Spectral Analysis Identifies Sites of High-Frequency Activity Maintaining Atrial Fibrillation in Humans. Circulation, 112(6), 789-797. doi:10.1161/circulationaha.104.517011Mansour, M., Mandapati, R., Berenfeld, O., Chen, J., Samie, F. H., & Jalife, J. (2001). Left-to-Right Gradient of Atrial Frequencies During Acute Atrial Fibrillation in the Isolated Sheep Heart. Circulation, 103(21), 2631-2636. doi:10.1161/01.cir.103.21.2631Jalife, J. (2002). Mother rotors and fibrillatory conduction: a mechanism of atrial fibrillation. Cardiovascular Research, 54(2), 204-216. doi:10.1016/s0008-6363(02)00223-7Baykaner, T., Rogers, A. J., Meckler, G. L., Zaman, J., Navara, R., Rodrigo, M., … Heidenreich, P. A. (2018). Clinical Implications of Ablation of Drivers for Atrial Fibrillation. Circulation: Arrhythmia and Electrophysiology, 11(5). doi:10.1161/circep.117.006119Zaman, J. A. B., Sauer, W. H., Alhusseini, M. I., Baykaner, T., Borne, R. T., Kowalewski, C. A. B., … Peters, N. S. (2018). Identification and Characterization of Sites Where Persistent Atrial Fibrillation Is Terminated by Localized Ablation. Circulation: Arrhythmia and Electrophysiology, 11(1). doi:10.1161/circep.117.005258Martinez-Mateu, L., Romero, L., Ferrer-Albero, A., Sebastian, R., Rodríguez Matas, J. F., Jalife, J., … Saiz, J. (2018). Factors affecting basket catheter detection of real and phantom rotors in the atria: A computational study. PLOS Computational Biology, 14(3), e1006017. doi:10.1371/journal.pcbi.1006017Identification of Rotors during Human Atrial Fibrillation Using Contact Mapping and Phase Singularity Detection: Technical Considerations. (2017). IEEE Transactions on Biomedical Engineering, 64(2), 310-318. doi:10.1109/tbme.2016.2554660Podziemski, P., Zeemering, S., Kuklik, P., van Hunnik, A., Maesen, B., Maessen, J., … Schotten, U. (2018). Rotors Detected by Phase Analysis of Filtered, Epicardial Atrial Fibrillation Electrograms Colocalize With Regions of Conduction Block. Circulation: Arrhythmia and Electrophysiology, 11(10). doi:10.1161/circep.117.005858ALHUSSEINI, M., VIDMAR, D., MECKLER, G. L., KOWALEWSKI, C. A., SHENASA, F., WANG, P. J., … RAPPEL, W.-J. (2017). Two Independent Mapping Techniques Identify Rotational Activity Patterns at Sites of Local Termination During Persistent Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 28(6), 615-622. doi:10.1111/jce.13177Rodrigo, M., Climent, A. M., Liberos, A., Fernández-Avilés, F., Berenfeld, O., Atienza, F., & Guillem, M. S. (2017). Technical Considerations on Phase Mapping for Identification of Atrial Reentrant Activity in Direct- and Inverse-Computed Electrograms. Circulation: Arrhythmia and Electrophysiology, 10(9). doi:10.1161/circep.117.005008Kowalewski, C. A. B., Shenasa, F., Rodrigo, M., Clopton, P., Meckler, G., Alhusseini, M. I., … Narayan, S. M. (2018). Interaction of Localized Drivers and Disorganized Activation in Persistent Atrial Fibrillation. Circulation: Arrhythmia and Electrophysiology, 11(6). doi:10.1161/circep.117.005846Schotten, U., Verheule, S., Kirchhof, P., & Goette, A. (2011). Pathophysiological Mechanisms of Atrial Fibrillation: A Translational Appraisal. Physiological Reviews, 91(1), 265-325. doi:10.1152/physrev.00031.2009Laughner, J., Shome, S., Child, N., Shuros, A., Neuzil, P., Gill, J., & Wright, M. (2016). Practical Considerations of Mapping Persistent Atrial Fibrillation With Whole-Chamber Basket Catheters. JACC: Clinical Electrophysiology, 2(1), 55-65. doi:10.1016/j.jacep.2015.09.017Gray, R. A., Pertsov, A. M., & Jalife, J. (1998). Erratum: Spatial and temporal organization during cardiac fibrillation. Nature, 393(6681), 191-191. doi:10.1038/30290Allessie, M., & de Groot, N. (2014). CrossTalk opposing view: Rotors have not been demonstrated to be the drivers of atrial fibrillation. The Journal of Physiology, 592(15), 3167-3170. doi:10.1113/jphysiol.2014.271809Atienza, F., Calvo, D., Almendral, J., Zlochiver, S., Grzeda, K. R., Martínez-Alzamora, N., … Berenfeld, O. (2011). Mechanisms of Fractionated Electrograms Formation in the Posterior Left Atrium During Paroxysmal Atrial Fibrillation in Humans. Journal of the American College of Cardiology, 57(9), 1081-1092. doi:10.1016/j.jacc.2010.09.066Breiman, L. (2001). Machine Learning, 45(1), 5-32. doi:10.1023/a:101093340432

Impact of spill-in counts from off-target regions on [18F]Flortaucipir PET quantification.

[18F]Flortaucipir (FTP) PET quantification is usually hindered by spill-in counts from off-target binding (OFF) regions. The present work aims to provide an in-depth analysis of the impact of OFF in FTP PET quantification, as well as to identify optimal partial volume correction (PVC) strategies to minimize this problem. 309 amyloid-beta (Aβ) negative cognitively normal subjects were included in the study. Additionally, 510 realistic FTP images with different levels of OFF were generated using Monte Carlo simulation (MC). Images were corrected for PVC using both a simple two-compartment and a multi-region method including OFF regions. FTP standardized uptake value ratio (SUVR) was quantified in Braak Areas (BA), the hippocampus (which was not included in Braak I/II) and different OFF regions (caudate, putamen, pallidum, thalamus, choroid plexus (ChPlex), cerebellar white matter (cerebWM), hemispheric white matter (hemisWM) and cerebrospinal fluid (CSF)) using the lower portion of the cerebellum as a reference region. The correlations between OFF and cortical SUVRs were studied both in real and in simulated PET images, with and without PVC. In-vivo, we found correlations between all OFF and target regions, especially strong for the hemisWM (slope>0.63, R2>0.4). All the correlations were attenuated but remained significant after applying PVC, except for the ChPlex. In MC simulations, the hemisWM and CSF were the main contributors to PVE in all BA (slopes 0.15-0.26 and 0.13-0.21 respectively). The hemisWM (slope=0.2), as well as the ChPlex (slope=0.02), influenced SUVRs in the hippocampus. The CerebWM was negatively correlated with all target regions (slope0.63, R2>0.4). All the correlations were attenuated but remained significant after applying PVC, except for the ChPlex. In MC simulations, the hemisWM and CSF were the main contributors to PVE in all BA (slopes 0.15-0.26 and 0.13-0.21 respectively). The hemisWM (slope=0.2), as well as the ChPlex (slope=0.02), influenced SUVRs in the hippocampus. The CerebWM was negatively correlated with all target regions (slope0.4). All the correlations were attenuated but remained significant after applying PVC, except for the ChPlex. In MC simulations, the hemisWM and CSF were the main contributors to PVE in all BA (slopes 0.15-0.26 and 0.13-0.21 respectively). The hemisWM (slope=0.2), as well as the ChPlex (slope=0.02), influenced SUVRs in the hippocampus. The CerebWM was negatively correlated with all target regions (slope0.8). While no other correlations between OFF and target regions were found, hemisWM was correlated with all OFF regions but the cerebWM (slopes 0.06-0.33). HemisWM correlations attenuated (slopes HemisWM is the main driver of spill-in effects in FTP PET, affecting both target regions and the rest of OFF regions. PVC successfully reduces PVE, even when using a simple two-compartment method. Despite PVC, non-zero correlations were still observed between target and OFF regions in vivo, which suggests the existence of biological or tracer-related contributions to these correlations