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12. An optimized protocol for correlation of PET-FDG and pCASL data in mild cognitive impairment (MCI) patients

Author

Cerina, V, De Bernardi, E, Bigiogera, V, JONGHI - LAVARINI, L, Pozzi, F, Crivellaro, C, Morzenti, S, Moresco, R, Basso, G, Cerina, V, De Bernardi, E, Bigiogera, V, JONGHI - LAVARINI, L, Pozzi, F, Crivellaro, C, Morzenti, S, Moresco, R, and Basso, G

Subjects
Mild Cognitive Impairment, Brain 18F-FDG PET, Dementia, ROI-based quantitative analysis, Arterial Spin Labeling
Abstract

Introduction: Recent development of anti-βamyloid drugs for dementigenic neurodegenerative diseases treatment necessitates identification of target patients in MCI stage. Clinical framing also relies on the identification of brain hypometabolism patterns suggestive of neurodegeneration detected by PET-FDG. New MRI perfusion methods such pseudo Continuous Arterial Spin Labeling (pCASL) that do not require contrast medium make it possible adding perfusion data to biomarkers useful for diagnosis. A study to define an optimized protocol analysis was conducted, to investigate the correlation between FDG-PET and pCASL information. Material and Methods: FDG-PET, pCASL and structural MR images were acquired from 15 patients (mean age 76 yr.). To validate the present analysis with a standard group analysis, a sample of 111 healthy subjects FDG-PET scans underwent the same processing. Starting from a standard SPM12 pipeline and using customized Matlab routines, an optimized protocol of preprocessing and ROI-based analysis were defined. Results: PET, pCASL and MR were normalized in MNI space and smoothed. A better spatial normalization for pCASL scans was obtained using the source image. Considering PET/pCASL low spatial resolution, different methods of Gray Matter (GM) segmentation were compared. A mean tissue probability map of GM, obtained from 662 healthy elderly subjects in the same patients range of age, was considered and used also for PVE correction in PET scans. For patients, GM obtained using the template was compared with the segmented one from the T1-weighted image to evaluate the eventual atrophy degree or possible cortex reduction due to incomplete atlas-patient cortex superimposition. Standardized Uptake Values (SUVr) from FDG-PET and Cerebral Blood Flow values (CBFr) values form pCASL, both normalized on cerebellar mean values, were calculated for all the 88 cortical regions of the Automated Anatomic Labeling template version 3 (AAL3) and for the 22 macro-regions obtained by combining sub-areas of AAL3. Discussion: According to this optimized protocol, further analysis on images are now being conducted. They will lead to the investigation of correlation between SUVr and CBFr values in the 88 regions and in the 22 macro-regions through Pearson coefficients, histograms and pattern similarities. A validation of the present analysis with the standard spm12 one was also conducted.

Published
2022

13. Validation of brain 18FDG-PET and pCASL joint analysis tool: a ROI-based approach

Author

Cerina, V, De Bernardi, E, Bigiogera, V, Jonghi - Lavarini, L, Pozzi, F, Crivellaro, C, Morzenti, S, Apollonio, I, Ferrarese, C, Moresco, R, Basso, G, Cerina, V, De Bernardi, E, Bigiogera, V, Jonghi - Lavarini, L, Pozzi, F, Crivellaro, C, Morzenti, S, Apollonio, I, Ferrarese, C, Moresco, R, and Basso, G

Subjects
Mild Cognitive Impairment, Brain 18F-FDG PET, Dementia, ROI-based quantitative analysi, Arterial Spin Labeling, Statistical Parametric Mapping (SPM)
Abstract

Introduction: Multimodal neuroimaging techniques allow to adequately address diagnosis questions issued by clinicians and researchers about human brain behavior. Multimodality means combining different type of information coming from functional and morpho-structural images. This is particularly important in case of neurodegenerative diseases, starting at Mild Cognitive Impairment (MCI) stage, ending to the effective progression to dementia. Brain hypometabolism patterns detected by 18FDG-PET can be combined with hypoperfusion information that nowadays can be non-invasively acquired with new MRI functional sequences, such as pseudo Continuous Arterial Spin Labeling (pCASL). This may allow pCASL to easily become an additional biomarker for diagnosis of dementia. A joint PET-pCASL analysis tool, optimized in preprocessing, was developed and then validated versus the conventional SPM12 toolbox. Material and Methods: An optimized protocol of preprocessing and ROI-based analysis was defined, starting from an SPM12 standard pipeline and using customized Matlab routines. Volumes were all normalized in MNI space. Normalization parameters for pCASL images were defined on the high resolution source image, co-registered to the T1-weigthed image. A mean Gray Matter (GM) tissue probability map, obtained from 662 healthy subjects in the patients range of age, was used for GM segmentation and for PVE correction in 18FDG-PET scans. The developed tool was validated on 20 MCI patients (mean age 76 yr.), assessing outcomes agreement vs a standard SPM12 analysis, using a single subject versus group analysis. This validation was performed on 18FDG-PET data only, where a sample of 111 healthy subjects 18FDG-PET scans was available as control group. In the SPM analysis a general linear model was applied, age was considered as covariate, and significance level was set at 0.05 (FWE-corrected) at a cluster level. Indirect validation for pCASL data, where normative data and a control group were not available, was derived by cross-correlation with 18FDG-PET results. Results: 18FDG-PET Standardized Uptake Values (SUVr) and pCASL Cerebral Blood Flow values (CBFr), both normalized on cerebellar mean values, were calculated in 22 macro-regions obtained by combining sub-areas of the Automated Anatomic Labeling template version 3 (AAL3). For 18FDG-PET, regions that fall outside normality range were the same found to belong to signifi cant clusters in the SPM referenceoutcome. Thereby, a comparison between 18FDG-PET and pCASL relying on SUVr and CBFr values incorresponding regions can be assessed (Fig. 1b). Both regional values and relative ratios between region scan be evaluated. Discussion: The validation of our tool on 18FDG-PET will allow it to be used for further investigation of correlation between SUVr and CBFr values in the 22 macro-regions. References: [1] Y. H. K. Cha, M. A. Jog, Y. C. Kim, S. Chakrapani, S. M. Kraman, and D. J. J. Wang, “Regional correlation between resting state FDG PET and pCASL perfusion MRI,” J. Cereb. Blood Flow Metab., vol. 33, no. 12, pp.1909–1914, Dec. 2013. [2] L. Yan et al., “Regional association of pCASL-MRI with FDG-PET and PiB-PET in people at risk for autosomal dominant Alzheimer’s disease,” NeuroImage. Clin., vol. 17, pp. 751–760, 2017.

Published
2022

16. CD56, HLA-DR, and CD45 recognize a subtype of childhood AML harboring CBFA2T3-GLIS2 fusion transcript

Author

Zangrando, A., Cavagnero, F., Scarparo, P., Varotto, E., Francescato, S., Tregnago, C., Cuccurullo, R., Fagioli, F., Nigro, L. L., Masetti, R., Putti, M. C., Rizzari, C., Santoro, N., Pession, A., Pigazzi, M., Locatelli, F., Basso, G., Buldini, B., Zangrando, A, Cavagnero, F, Scarparo, P, Varotto, E, Francescato, S, Tregnago, C, Cuccurullo, R, Fagioli, F, Nigro, L, Masetti, R, Putti, M, Rizzari, C, Santoro, N, Pession, A, Pigazzi, M, Locatelli, F, Basso, G, Buldini, B, Zangrando A., Cavagnero F., Scarparo P., Varotto E., Francescato S., Tregnago C., Cuccurullo R., Fagioli F., Nigro L.L., Masetti R., Putti M.C., Rizzari C., Santoro N., Pession A., Pigazzi M., Locatelli F., Basso G., and Buldini B.

Subjects
Oncogene Proteins, Fusion, Brief Report, HLA-DR Antigens, acute myeloid leukemia, Repressor Proteins, CBFA2T3‐GLIS2, Leukemia, Myeloid, Acute, computational analysi, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, immunophenotyping, computational analysis, hemic and lymphatic diseases, Humans, CBFA2T3-GLIS2, Child, Transcriptome
Abstract

The presence of CBFA2T3‐GLIS2 fusion gene has been identified in childhood Acute Myeloid Leukemia (AML). In view of the genomic studies indicating a distinct gene expression profile, we evaluated the role of immunophenotyping in characterizing a rare subtype of AML‐CBFA2T3‐GLIS2 rearranged. Immunophenotypic data were obtained by studying a cohort of 20 pediatric CBFA2T3‐GLIS2‐AML and 77 AML patients not carrying the fusion transcript. Enrolled cases were included in the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP) AML trials and immunophenotypes were compared using different statistical approaches. By multiple computational procedures, we identified two main core antigens responsible for the identification of the CBFA2T3‐GLIS2‐AML. CD56 showed the highest performance in single marker evaluation (AUC = 0.89) and granted the most accurate prediction when used in combination with HLA‐DR (AUC = 0.97) displaying a 93% sensitivity and 99% specificity. We also observed a weak‐to‐negative CD45 expression, being exceptional in AML. We here provide evidence that the combination of HLA‐DR negativity and intense bright CD56 expression detects a rare and aggressive pediatric AML genetic lesion improving the diagnosis performance.

Published
2021

46. Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia

Author

Flohr, T, Schrauder, A, Cazzaniga, G, Panzer-Grümayer, R, van der Velden, V, Fischer, S, Stanulla, M, Basso, G, Niggli, F K, Schäfer, B W, Sutton, R, Koehler, R, Zimmermann, M, Valsecchi, M G, Gadner, H, Masera, G, Schrappe, M, van Dongen, J J M, Biondi, A, and Bartram, C R

Published
2008
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