Skip to main content
European Commission logo print header

Enhancement of clinical value of functional imaging through automated removal of partial volume effect

Exploitable results

PVELab is a software tool for the integrated analysis of brain PET/SPET and MRI studies. It comprise at least one module for each step needed to correct Nuclear Medicine data for partial volume effect, and software interfaces to use alternative widespread software modules. It includes interfaces so the methods can be used with data formatted in the Analyze and DICOM data format. In particular PVELab includes: Fileload: Software for loading and converting Analyze and DICOM image files, developed in collaboration by NRU, Neurobiology Research Unit, Copenhagen and IBB, Biostructure and Bioimaging Institute, Naples. Registration: - Interactive Image Overlay developed by NRU. - Interactive Point Selection developed by NRU. - Interface to SPM co-registration (Statistical Parametric Mapping, Functional Imaging Laboratory, London). - Interface to AIR registration (Automatic Image Registration, Laboratory of Neuroimaging, UCLA, Los Angeles). - Load AIR file developed by NRU. Segmentation: - QMCI segmentation developed by IBB. - Interface to SPM segmentation (Statistical Parametric Mapping). - Interface to BrainSeg segmentation (KIMSH, University of Kent at Canterbury). - Load segmentation volume. Reslice: - Interface to ResliceWarp (Brain Warp, Informatics and Mathematical Modelling, DTU, Lyngby, Copenhagen). - Interface to AIR reslicing (Automatic Image Registration). Reslice developed by NRU Atlas (modules for automated definition of volumetric regions of interest (ROI)): - Talairach based developed by IBB. - MNI based developed by IBB and Inserm. - Applyrois interface developed by NRU. PVE correction: Partial volume effect correction (PVEc), developed by IBB, following the methods described by Meltzer et al. [J Comput Assist Tomogr 1990;14:561-570] (M PVEc), Müller-Gärtner et al. [J Cereb Blood Flow Metab 1992;12:571-583] (MG PVEc), Rousset et al. [J Nucl Med 1998;39:904-911] (R PVEc), plus a modified version of MG PVEc (mMG PVEc) which uses the WM estimate from R PVEc. The main program and GUI were written by NRU using Matlab, a programming tool widely diffused in the biomedical imaging. The software allows to apply a set of labels, defined a priori in the Talairach space to the segmented co-registered MRI [NeuroImage 2002;17:373-384]. Resulting ROIs are then transferred onto the PET/SPET study, and corresponding values are corrected according to R PVEc, as well as onto the images obtained by M PVEc, MG PVEc and mMG PVEc, providing corresponding corrected values. The software also includes: - An original PVE-correction technique achieved by IBB. - An original tool for fully automated definition of PVE-corrected white matter value. - A fully automated Volume of Interest definition method, which now allows also a fully automated definition, when a normalisation matrix is available from external software (e.g. SPM). The results of the validation are reported in the paper by Quarantelli et al., entitled "An integrated software for the analysis of brain PET/SPECT studies with Partial Volume Effect Correction", published by the Journal of Nuclear Medicine (J Nucl Med. 2004 Feb; 45(2): 192-201). In this work accuracy and precision of these methods have been measured applying the software to four simulated FDG-PET studies and subsequently introducing larger experimental errors, including co-registration errors (0 to 6 pixel mis-registration), segmentation errors (-13.7% to +14.1% GM volume change) and resolution estimate errors (-16.9% to 26.8% FWHM mismatch). Even in absence of segmentation and co-registration errors, the uncorrected PET values showed -37.6% GM underestimation and 91.7% WM overestimation. M PVEc left a residual underestimation of GM values (-21.2%). Application of R PVEc and mMG PVEc provided accuracy above 96%. Software documentation has been included in SW package, and is being upgraded according to feedback from end-users. The software has been tested through fully and is in use in XX different research centres selected as Beta test sites. Research centres can ask to download the software to act as beta sites (http://nru.dk/publications/pveout, password required, send email to pvelab@nru.dk). PVEOut consortium adopted the policy of create some beta cites in research centres to increase the initial core of users thus increasing the industrial interest of the PVEOut results.
Application of the software tools developed by PVEOut to the data sets available within the consortium have provided preliminary results in several pathologies. The implementation of a multiparametric segmentation technique capable of segmenting multiple sclerosis lesions, beside the apparently normal brain tissues, was applied to 50 patients with Relapsing-remitting multiple sclerosis (RR-MS) and to 54 NV, allowed to demonstrate that brain atrophy in RR-MS is mainly related to GM loss, and correlating to faWM [Quarantelli M, et al. Neuroimage 2003;18:360]. A similar analysis carried out in 6 patients with CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) [Quarantelli M, et al. ISMRM Proceedings 2001, abs. 1452] demonstrated the applicability of the same techniques to the analysis of brain MRI from patients with cerebrovascular disorders and the lack of correlation between brain atrophy and ischemic lesion load in CADASIL. The application of the methods for brain MRI segmentation and automated volume of interest (VOI) definition to MRI studies of 25 normal volunteers (NV), 14 patients with deficit schizophrenia (DS) and 14 with non-deficit schizophrenia (NDS), allowed to confirm the atrophy in schizophrenic patients, and to highlight structural greater structural brain abnormalities in NDS, adding to the evidence that deficit schizophrenia does not represent just the more severe end of a schizophrenia continuum [Quarantelli M , et al. NeuroImage 2002;17:373]. While the conventional analysis of SPET CBF studies from 8 patients with fronto-temporal dementia (FTD) and of 21 AD patients confirmed the preferential involvement of the frontotemporal regions in FTD patients and of the temporoparietal regions in AD patients [Varrone A, et al. Eur J Nucl Med Mol Imaging 2002;29:1447], an analysis with PVE-correction of 10 AD patients compared to 12 subjects with Mild Cognitive Impairment (MCI) [Quarantelli M, et al. Proc. of the 2004 meeting of the Organisation for Human Brain Mapping], beside confirming the involvement of temporal lobes and fronto-parietal association cortex in AD, showed that only the decreases in posterior cingulate remained significant after PVE-correction. A similar finding was obtained when analysing FDG-PET studies from 23 mild AD patients and 13 aged NV [K Berkouk, et al. Proc. of the 2003 meeting of the Organisation for HBM; Abtract No. 1017]. Furthermore, an analysis with PVE-correction of SPECT studies of GABA-receptors (a synaptic marker) in 5 AD patients 8 MCI patients and 3 NV demonstrated, before PVE-correction, a significant fronto-temporo-parietal cortical reduction bilaterally, in AD vs. both MCI and NV, while after PVE-correction this decrease remained significant in posterior cingulate, suggesting that the reduction in cGABA-receptors in AD parallels but also exceeds structural changes as measured by MRI segmentation [Pappatà S, et al. Proc. of the 2004 meeting of the Organisation for Human Brain Mapping]. A novel method for analysing FDG uptake and underlying brain tissue volumes was also developed and applied to PET studies from 18 NV, showing a relative hyper-activity, as compared to GM volume, of most GM structures of the dorsal part of the brain, except the thalamus, and a relative hypo-activity, as compared to GM volume, of the hippocampus and the cerebellum, consistent with autoradiographic data from non-human primates [K. Berkouk, et al. Proc. of the 2002 meeting of the Organisation for Human Brain Mapping; Abstr. No. 10127]. Regarding Neuroreceptor PET studies, PVE correction software was also used to evaluate the impact of partial volume effect on the quantification of dopamine-D2 receptors with PET using the high-affinity radioligand [11C]FLB 457, and to identify those receptor-binding parameters most and least susceptible to PVE. Also the performances of different PVE correction algorithms were compared, to identify the most suitable for imaging of dopaminergic tracers. This study confirmed that the regions most susceptible to PVE are the small or thin regions (amygdala and temporal cortex). Vd was much more underestimated (increased up to +55% when PVE correction was applied) without PVE correction than BP (changes with PVE-correction ranging between -10 and +10%). Comparison of different PVE-correction techniques implemented in PVELab proved the ROI method to be the most suitable technique for PVE correction in dopamine-receptor imaging.
We have realised an anthropomorphic multi-compartment phantom of the human brain suitable for PET/SPET and CT/MR imaging. No other phantom with these characteristics has either been described in the refereed literature or is currently commercially available. The phantom (which we call STEPBrain) was designed as composed by two separate compartments for grey matter (GM) and white matter (WM), which can be filled by solutions with different isotope (PET/SPET), metal (MRI), or iodine (CT) concentrations. It was built by a rapid prototyping technique applied to a digital model derived from a 1.5T MRI dataset of a 35 y.o. normal volunteer composed of 150 3mm-thick partially overlapping slices (1mm increment) covering the whole brain. For each slice location T1-, PD- and T2- weighted spin-echo images were obtained, and segmented into GM, WM and CSF using a multi-parametric technique (Magn Reson Med 1997;37:84). The subsequent processing of the segmented images by homemade and industrial software included: manual editing of the basal ganglia to ensure their connection with GM to allow proper filling; filling of the vessels located inside the parenchyma with the tissue type that occur most frequently on the surrounding pixels; final elimination of "isles" of pixels inside a tissue type not connected in 3-D with other pixels of the same type; a 5x5x3 median spatial filtering of the entire volume to smooth the boundaries of the tissues; conversion of the binary file into a vectorial representation of the surfaces; creation of the hollow of GM and WM compartments defining the separation 1.5mm-thick walls separating the three compartments; adding of tubes to allow filling of GM and WM compartments. The resulting file was used to drive a rapid prototyping machine, which, materialising the walls, provides the final phantom. GM and WM compartments are fillable with solutions with different isotope concentrations for PET/SPET scanning (i.e. 4/1 ratio simulates normal GM/WM contrast for FDG), while different paramagnetic ion concentrations can simulate different GM/WM relaxometric properties. The prototype of the phantom proved to be waterproof, with no communication between GM and WM compartments, and suitable for CT, MR, PET and SPET scanning. An important application, which is the original aim of this phantom, is the validation of different techniques for partial volume effect correction in low-resolution images. STEPBrain is currently the only anthropomorphic phantom useful for this aim. Furthermore STEPBrain can be used for NM brain study simulation better then other anthropomorphic brain phantoms, currently in use in most NM centres. The most widespread of them is the Hoffman phantom realised with shaped thin plastic levels inserted in a plastic cylinder. It comprises only one compartment simulating the brain. GM area is empty, while WM area is in part (3/4) packed by plastic levels to simulate a WM concentration of 1/4 of GM concentration. Since in STEPBrain GM and WM are two independent compartments, it can simulate any ratio of isotope concentration. The industrial cost of STEPBrain is about 1/5 of the mean price of the other anthropomorphic phantoms used in Nuclear Medicine. The potential market is very large, corresponding to all NM departments.

Searching for OpenAIRE data...

There was an error trying to search data from OpenAIRE

No results available