Pierre Malick Koulibaly

Perfusion Brain SPECT and Statistical Parametric Mapping Analysis Indicate That Apathy Is a Cingulate Syndrome: A Study in Alzheimer's Disease and Nondemented Patients

Apathy is the most frequent behavioral symptom in Alzheimers disease and is also frequently reported in other brain organic disorders occurring in the elderly. Based on the literature, we hypothesized that apathy was related to an anterior cingulate hypofunction. Forty-one subjects were studied. According to ICD 10 diagnostic criteria, 28 patients had Alzheimer dementia (demented: diagnostic group 1), and 13 had organic personality disorders or mild cognitive impairment not attributable to dementia (nondemented: diagnostic group 2). Apathy was evaluated by the Neuro-Psychiatric Inventory. As a result each diagnostic group was divided into two symptomatic subgroups: apathetic or nonapathetic. Brain perfusion was measured by (99m)Tc-labeled bicisate (ECD) brain SPECT and the images were compared using Statistical Parametric Mapping (SPM96). We began by comparing apathetic vs nonapathetic patients, whatever their diagnostic group (whole population), then analyzed them within each group. Twenty-one subjects were apathetic (14 in group 1 and 7 in group 2) and 20 were not (14 in group 1 and 6 in group 2). For the whole population, the Z map showed a significant decrease in ECD uptake for the apathetic patients in the anterior cingulate (P < 0.002) bilaterally. This area was also identified as hypoactive by SPM analysis in the demented (P < 0.035) and in the nondemented (P < 0.02) apathetic patient groups. Finally, conjunction analysis indicated that the anterior cingulate was the common hypoactive structure of the two apathetic subgroups (Z = 4.35, P < 0.0009). These results point to a close relationship between apathy and the anterior cingulate region.

Brain perfusion in Alzheimer's disease with and without apathy: a SPECT study with statistical parametric mapping analysis.

Alzheimers disease (AD) is clinically characterized by cognitive symptoms that, in combination with behavioral disturbances, significantly interfere with activities of daily living. These behavioral disorders contribute to the clinical heterogeneity of the disease and probably express different pathophysiological processes. Apathy is one of the most frequent behavioral disorders in AD. The aim of this study was to evaluate brain perfusion of AD patients with and without apathy (as determined by the Neuropsychiatric Inventory) compared with that in healthy elderly subjects. A total of 15 AD patients without apathy (AD/NA; mean age 76.6) and 15 AD patients with apathy (AD/A; mean age 77.6) were studied. Brain perfusion was measured by 99mTc-labeled bicisate (ECD) single-photon emission tomography (ECD SPECT). The images of the two AD subgroups were compared by means of statistical parametric mapping (SPM 99) to corresponding images of 11 healthy elderly control subjects (obtained from the Society of Nuclear Medicine database). Compared with the healthy elderly subjects, the apathy-free AD subgroup had significantly lower perfusion of inferior temporal regions (left fusiform gyrus, left parahippocampal area) and occipital regions (left gyrus lingualis). The apathy subgroup had significantly decreased perfusion of the left anterior cingulate, the right inferior and medial gyrus frontalis, the left orbitofrontal gyrus and the right gyrus lingualis. The differences in the brain areas with reduced perfusion between the apathy-free subjects (mainly the posterior regions) and the apathetic subjects (mainly the anterior regions) indicate that behavioral disorders such as apathy participate in the heterogeneity of brain perfusion in AD.

Model-based respiratory motion compensation for emission tomography image reconstruction

In emission tomography imaging, respiratory motion causes artifacts in lungs and cardiac reconstructed images, which lead to misinterpretations, imprecise diagnosis, impairing of fusion with other modalities, etc. Solutions like respiratory gating, correlated dynamic PET techniques, list-mode data based techniques and others have been tested, which lead to improvements over the spatial activity distribution in lungs lesions, but which have the disadvantages of requiring additional instrumentation or the need of discarding part of the projection data used for reconstruction. The objective of this study is to incorporate respiratory motion compensation directly into the image reconstruction process, without any additional acquisition protocol consideration. To this end, we propose an extension to the maximum likelihood expectation maximization (MLEM) algorithm that includes a respiratory motion model, which takes into account the displacements and volume deformations produced by the respiratory motion during the data acquisition process. We present results from synthetic simulations incorporating real respiratory motion as well as from phantom and patient data.

Calibration of gamma camera systems for a multicentre European 123I-FP-CIT SPECT normal database

PurposeA joint initiative of the European Association of Nuclear Medicine (EANM) Neuroimaging Committee and EANM Research Ltd. aimed to generate a European database of [123I]FP-CIT single photon emission computed tomography (SPECT) scans of healthy controls. This study describes the characterization and harmonization of the imaging equipment of the institutions involved.Methods123I SPECT images of a striatal phantom filled with striatal to background ratios between 10:1 and 1:1 were acquired on all the gamma cameras with absolute ratios measured from aliquots. The images were reconstructed by a core lab using ordered subset expectation maximization (OSEM) without corrections (NC), with attenuation correction only (AC) and additional scatter and septal penetration correction (ACSC) using the triple energy window method. A quantitative parameter, the simulated specific binding ratio (sSBR), was measured using the “Southampton” methodology that accounts for the partial volume effect and compared against the actual values obtained from the aliquots. Camera-specific recovery coefficients were derived from linear regression and the error of the measurements was evaluated using the coefficient of variation (COV).ResultsThe relationship between measured and actual sSBRs was linear across all systems. Variability was observed between different manufacturers and, to a lesser extent, between cameras of the same type. The NC and AC measurements were found to underestimate systematically the actual sSBRs, while the ACSC measurements resulted in recovery coefficients close to 100% for all cameras (AC range 69–89%, ACSC range 87–116%). The COV improved from 46% (NC) to 32% (AC) and to 14% (ACSC) (p < 0.001).ConclusionA satisfactory linear response was observed across all cameras. Quantitative measurements depend upon the characteristics of the SPECT systems and their calibration is a necessary prerequisite for data pooling. Together with accounting for partial volume, the correction for scatter and septal penetration is essential for accurate quantification.

Classification of SPECT Images of Normal Subjects versus Images of Alzheimer's Disease Patients

This work aims at providing a tool to assist the interpretation of SPECT images for the diagnosis of Alzheimers Disease (AD). Our approach is to test classifiers, which uses the intensity values of the images, without any prior information. Such a classifier is built upon a training set, containing images with two different labels (AD patients and normal subjects). It will then provide a classification for any new unknown image. The main problem to be handled is the small number of available images compared to the large number of features (here the images voxels): the so-called small sample size problem. We evaluate here the ability of two linear classifiers to correctly label a set of 79 images. Our experiments show promising results. They also show that image classification based on intensity values only is possible and might be used for other applications as well.

Automatic Classification of SPECT Images of Alzheimer’s Disease Patients and Control Subjects

In this article we study the use of SPECT perfusion imaging for the diagnosis of Alzheimer’s disease. We present a classifier based approach that does not need any explicit knowledge about the pathology. We directly use the voxel intensities as features. This approach is compared with three classical approaches: regions of interests, statistical parametric mapping and visual analysis which is the most commonly used method. We tested our method both on simulated and on real data. The realistic simulations give us total control about the ground truth. On real data, our method was more sensitive than the human experts, while having an acceptable specificity. We conclude that an automatic method can be a useful help for clinicians.

Proposal for the standardisation of multi-centre trials in nuclear medicine imaging: prerequisites for a European 123I-FP-CIT SPECT database.

PurposeMulti-centre trials are an important part of proving the efficacy of procedures, drugs and interventions. Imaging components in such trials are becoming increasingly common; however, without sufficient control measures the usefulness of these data can be compromised. This paper describes a framework for performing high-quality multi-centre trials with single photon emission computed tomography (SPECT), using a pan-European initiative to acquire a normal control dopamine transporter brain scan database as an example.MethodsA framework to produce high-quality and consistent SPECT imaging data was based on three key areas: quality assurance, the imaging protocol and system characterisation. Quality assurance was important to ensure that the quality of the equipment and local techniques was good and consistently high; system characterisation helped understand and where possible match the performance of the systems involved, whereas the imaging protocol was designed to allow a degree of flexibility to best match the characteristics of each imaging device.ResultsA total of 24 cameras on 15 sites from 8 different manufacturers were evaluated for inclusion in our multi-centre initiative. All results matched the required level of specification and each had their performance characterised. Differences in performance were found between different system types and cameras of the same type. Imaging protocols for each site were modified to match their individual characteristics to produce comparable high-quality SPECT images.ConclusionA framework has been designed to produce high-quality data for multi-centre SPECT studies. This framework has been successfully applied to a pan-European initiative to acquire a healthy control dopamine transporter image database.

Partial volume effect correction in SPECT for striatal uptake measurements in patients with neurodegenerative diseases: impact upon patient classification

PurposeIn single-photon emission computed tomography (SPECT) of the dopaminergic system, measurements of striatal uptake are useful for diagnosis and patient follow-up but are strongly biased by the partial volume effect (PVE). We studied whether PVE correction might improve patient classification based on binding potential (BP) measurements.MethodsPatients with a probable diagnosis of dementia with Lewy bodies (DLB, 10 patients) or Alzheimer’s disease (AD, 13 patients) were studied by 123I-FP-CIT SPECT. SPECT images were reconstructed with and without PVE correction. Each patient SPECT scan was also simulated to obtain SPECT data whose characteristics were fully known. In addition, 17 SPECT scans were simulated with striatal uptake values mimicking pre-symptomatic cases of DLB.ResultsWithout PVE correction, mean putamen BP values were 2.9±0.4 and 0.9±0.2 for AD and DLB patients respectively, while with PVE correction, they were 8.6±1.5 and 1.9±0.5 respectively. All patients were properly identified as having AD or DLB when considering mean putamen BP measured on their real or simulated SPECT scan, with and without PVE correction. All 30 simulations mimicking pre-symptomatic DLB and AD patients were accurately classified with PVE correction, but without PVE correction 15 mean putamen BP values were in a range where AD and DLB could not be distinguished.ConclusionWe conclude that putamen BP values measured without PVE correction can be used to differentiate probable DLB and AD due to the already severe reduction in dopamine transporter levels. PVE correction appeared useful for accurate differential diagnosis between AD and pre-symptomatic DLB.

Respiratory motion correction in emission tomography image reconstruction

In Emission Tomography imaging, respiratory motion causes artifacts in lungs and cardiac reconstructed images, which lead to misinterpretations and imprecise diagnosis. Solutions like respiratory gating, correlated dynamic PET techniques, list-mode data based techniques and others have been tested with improvements over the spatial activity distribution in lungs lesions, but with the disadvantages of requiring additional instrumentation or discarding part of the projection data used for reconstruction. The objective of this study is to incorporate respiratory motion correction directly into the image reconstruction process, without any additional acquisition protocol consideration. To this end, we propose an extension to the Maximum Likelihood Expectation Maximization (MLEM) algorithm that includes a respiratory motion model, which takes into account the displacements and volume deformations produced by the respiratory motion during the data acquisition process. We present results from synthetic simulations incorporating real respiratory motion as well as from phantom and patient data.

[(123)I]FP-CIT ENC-DAT normal database: the impact of the reconstruction and quantification methods.

Background[123I]FP-CIT is a well-established radiotracer for the diagnosis of dopaminergic degenerative disorders. The European Normal Control Database of DaTSCAN (ENC-DAT) of healthy controls has provided age and gender-specific reference values for the [123I]FP-CIT specific binding ratio (SBR) under optimised protocols for image acquisition and processing. Simpler reconstruction methods, however, are in use in many hospitals, often without implementation of attenuation and scatter corrections. This study investigates the impact on the reference values of simpler approaches using two quantifications methods, BRASS and Southampton, and explores the performance of the striatal phantom calibration in their harmonisation.ResultsBRASS and Southampton databases comprising 123 ENC-DAT subjects, from gamma cameras with parallel collimators, were reconstructed using filtered back projection (FBP) and iterative reconstruction OSEM without corrections (IRNC) and compared against the recommended OSEM with corrections for attenuation and scatter and septal penetration (ACSC), before and after applying phantom calibration. Differences between databases were quantified using the percentage difference of their SBR in the dopamine transporter-rich striatum, with their significance determined by the paired t test with Bonferroni correction.Attenuation and scatter losses, measured from the percentage difference between IRNC and ACSC databases, were of the order of 47% for both BRASS and Southampton quantifications. Phantom corrections were able to recover most of these losses, but the SBRs remained significantly lower than the “true” values (p < 0.001). Calibration provided, in fact, “first order” camera-dependent corrections, but could not include “second order” subject-dependent effects, such as septal penetration from extra-cranial activity. As for the ACSC databases, phantom calibration was instrumental in compensating for partial volume losses in BRASS (~67%, p < 0.001), while for the Southampton method, inherently free from them, it brought no significant changes and solely corrected for residual inter-camera variability (−0.2%, p = 0.44).ConclusionsThe ENC-DAT reference values are significantly dependent on the reconstruction and quantification methods and phantom calibration, while reducing the major part of their differences, is unable to fully harmonize them. Clinical use of any normal database, therefore, requires consistency with the processing methodology. Caution must be exercised when comparing data from different centres, recognising that the SBR may represent an “index” rather than a “true” value.