Ingeborg Goethals

99mTc-ECD brain perfusion SPET: variability, asymmetry and effects of age and gender in healthy adults.

Abstract. Reliable and high-resolution reference data for regional cerebral blood flow measured with single-photon emission tomography (SPET) are necessary for optimal clinical and research use. Therefore, a large dataset of normal technetium-99m labelled ethylene cysteine dimer (ECD) perfusion SPET in carefully screened healthy volunteers with an age range spanning six decades was created, with correction for non-uniform attenuation and scatter and based on an anatomically standardised analysis. Eighty-nine healthy volunteers, stratified for gender (46 females, 43 males; age 20–81 years), were included. Twelve volunteers underwent repeated 99mTc-ECD SPET after 2.5±2.3 weeks. An automated whole-brain volume of interest analysis with MANOVA as well as voxelwise analysis using SPM99 was conducted. Average intersubject variability was 4.8% while intrasubject reproducibility was 3.0%. An age-related decline in tracer uptake was found in the anterior cingulate gyrus, bilateral basal ganglia, left prefrontal, left lateral frontal and left superior temporal and insular cortex (all P=0.001–0.02). There was an overall increase in right/left asymmetry with age, which was most pronounced in the frontal and temporal neocortex. The most significant correlations between AI and age decade were found in the prefrontal (R=0.35, P=0.001) and superior temporal neocortex (R=0.43, P<0.001). Women had significantly higher uptake in the right parietal cortex (P<0.001), while men showed higher uptake in the cerebellum and the left anterior temporal and orbitofrontal cortex (all P<0.01). This normative dataset allows age- and gender-specific patient and group assessment of 99mTc-ECD perfusion SPET under a wide variety of clinical circumstances in relation to normal variations and highlights the importance of both age- and gender-specific normal datasets for optimal analysis sensitivity.

SPECT neuropsychological activation procedure with the Verbal Fluency Test in attempted suicide patients

Performance on the Verbal Fluency Test, as a measure of the ability of initiating processes, is reduced in depressed suicidal patients. The hampered results in this prefrontal executive task parallel the reduction in prefrontal blood perfusion and metabolism in depressed subjects. A neuropsychological activation study with the verbal fluency paradigm could evaluate a possible blunted increase in perfusion in the prefrontal cortex in depressed suicidal patients. Twenty clinically depressed patients who had recently attempted suicide and 20 healthy volunteers were included in a single photon emission computed tomography (SPECT) split-dose activation study following a verbal fluency paradigm. Statistical parametric mapping was used to determine voxelwise significant changes. Differences in regional cortical activation between the letter fluency and category fluency tasks in attempted suicide patients were found. These patients showed a blunted increase in perfusion in the prefrontal cortex. Methodological restrictions concerning group uniformity, medication bias and subjective effort of the participants are discussed. Our findings indicate a blunted increase in prefrontal blood perfusion as a possible biological reason for reduced drive and loss of initiative in attempted suicide patients.

Nuclear medicine imaging to predict response to radiotherapy: a review

PURPOSE To review available literature on positron emission tomography (PET) and single photon emission computerized tomography (SPECT) for the measurement of tumor metabolism, hypoxia, growth factor receptor expression, and apoptosis as predictors of response to radiotherapy. METHODS AND MATERIALS Medical literature databases (Pubmed, Medline) were screened for available literature and critically analyzed as to their scientific relevance. RESULTS Studies on 18F-fluorodeoxyglucose PET as a predictor of response to radiotherapy in head-and-neck carcinoma are promising but need confirmation in larger series. 18F-fluorothymine is stable in human plasma, and preliminary clinical data obtained with this marker of tumor cell proliferation are promising. For imaging tumor hypoxia, novel, more widely available radiopharmaceuticals with faster pharmacokinetics are mandatory. Imaging of ongoing apoptosis and growth factor expression is at a very early stage, but results obtained in other domains with radiolabeled peptides appear promising. Finally, for most of the tracers discussed, validation against a gold standard is needed. CONCLUSION Optimization of the pharmacokinetics of relevant radiopharmaceuticals as well as validation against gold-standard tests in large patient series are mandatory if PET and SPECT are to be implemented in routine clinical practice for the purpose of predicting response to radiotherapy.

Imaging of the 5-HT2A system: age-, gender-, and Alzheimer’s disease-related findings

Serotonin (5-HT) and more specifically the 5-HT(2A) receptor is involved in cognitive and non-cognitive behavior and plays an important role in Alzheimers disease (AD). The objective was to assess the 5-HT(2A) binding potential (BP) in healthy volunteers and AD with SPECT and 123I-5-I-R91150, a selective radio-iodinated 5-HT(2A) receptor antagonist. Twenty-six controls and nine AD patients were included. A semiquantitive analysis with normalization on cerebellar uptake provided estimates of BP for 26 cortical regions of interest. An age-related decline of neocortical BP was found (11.6% per decade). Compared to age-matched controls, a generally decreased neocortical BP in AD was found with a significant regional reduction in the orbitofrontal, prefrontal, lateral frontal, cingulate, sensorimotor, parietal inferior, and occipital region. These results are in line with previous postmortem, in vitro, and PET findings. The age-related decline highlights the necessity for matched advanced age study samples. The fact that the 5-HT(2A) receptor is differentially affected in AD patients has implications for both the etiological basis and therapeutic management of AD.

Brain perfusion SPECT in impulsivity-related personality disorders

BACKGROUND Impulsive behaviours in patients with cluster B personality disorders are associated with low glucose metabolism and regional cerebral blood flow in the frontal cortex and subcortical structures. The aim of this study is to confirm the presence of a particular pattern of brain perfusion in a sample of borderline (BPD) and anti-social personality disorder (ASPD) patients using brain perfusion single photon emission computed tomography (SPECT). METHODS A brain perfusion SPECT study was performed in 37 patients with BPD or ASPD (and no Axis I diagnosis) and 34 healthy control participants. Data were acquired on a triple head Toshiba gamma camera. Scatter and attenuation correction was done. Reconstructed SPECT images were analyzed by Statistical Parametrical Mapping (SPM99). RESULTS There were no significant differences in age and gender distributions between the patients and the healthy controls. With regard to the functional imaging results, patients were characterized by a reduced regional cerebral blood flow (rCBF) in right temporal and prefrontal brain areas, including the right lateral temporal cortex (BA 21), the right frontopolar cortex (BA 10) and the right ventrolateral prefontal cortex (BA 47). CONCLUSIONS Patients with BPD and ASPD who showed impulsive behaviour have diminished rCBF in areas of the right prefrontal and temporal cortex.

Gastrin-Releasing Peptide Receptor Imaging in Human Breast Carcinoma Versus Immunohistochemistry

This study reports on the uptake of 99mTc-RP527 by human breast carcinoma and its relationship to gastrin-releasing peptide receptor (GRP-R) expression as measured by immunohistochemistry (IHC). Methods: Nine patients referred because of a clinical diagnosis suggestive of breast carcinoma and 5 patients with tamoxifen-resistant bone-mestastasized breast carcinoma underwent 99mTc-RP527 scintigraphy. The findings were compared with routine staging examinations in all patients and with routine histology and IHC GRP-R staining in the first 9 patients. All 9 patients with suspected breast lesions were tumor positive. Results: The uptake of 99mTc-RP527 was evident in the primary tumor in 8 of 9 patients and in involved lymph nodes and part of the distant metastasis limited to the bone when present. 99mTc-RP527 uptake was not found in any of the tamoxifen-resistant patients. Conclusion: Uptake by primary breast carcinoma was significantly correlated with the presence of GRP-Rs as assessed by means of IHC.

PET with 18F-labelled choline-based tracers for tumour imaging: a review of the literature

PurposeTo give an up-to-date overview of the potential clinical utility of 18F-labelled choline derivatives for tumour imaging with positron emission tomography.MethodsA PubMed search for 18F-labelled choline analogues was performed. Review articles and reference lists were used to supplement the search findings.Results18F-labelled choline analogues have been investigated as oncological PET probes for many types of cancer on the basis of enhanced cell proliferation. To date, studies have focused on the evaluation of prostate cancer. Available studies have provided preliminary results for detecting local and metastatic disease. Experience with 18F-fluorocholine PET in other tumour types, including brain and liver tumours, is still limited. In the brain, excellent discrimination between tumour and normal tissue can be achieved due to the low physiological uptake of 18F-fluorocholine. In the liver, in which there is a moderate to high degree of physiological uptake in normal tissue, malignancy discrimination may be more challenging.ConclusionPET/CT with 18F-fluorocholine can be used to detect (recurrent) local prostate cancer, but seems to have limited value for T (tumour) and N (nodal) staging. In patients presenting with recurrent biochemical prostate cancer, it is a suitable single-step examination with the ability to exclude distant metastases when local salvage treatment is intended. In the brain, high-grade gliomas, metastases and benign lesions can be distinguished on the basis of 18F-fluorocholine uptake. Moreover, PET imaging is able to differentiate between radiation-induced injury and tumour recurrence. In the liver, 18F-fluorocholine PET/CT seems promising for the detection of hepatocellular carcinoma.

Efficiently updating and tracking the dominant kernel principal components

The dominant set of eigenvectors of the symmetrical kernel Gram matrix is used in many important kernel methods (like e.g. kernel Principal Component Analysis, feature approximation, denoising, compression, prediction) in the machine learning area. Yet in the case of dynamic and/or large-scale data, the batch calculation nature and computational demands of the eigenvector decomposition limit these methods in numerous applications. In this paper we present an efficient incremental approach for fast calculation of the dominant kernel eigenbasis, which allows us to track the kernel eigenspace dynamically. Experiments show that our updating scheme delivers a numerically stable and accurate approximation for eigenvalues and eigenvectors at every iteration in comparison to the batch algorithm.

The prefrontal cortex: insights from functional neuroimaging using cognitive activation tasks

This review presents neuroimaging studies which have explored the functional anatomy of a variety of cognitive processes represented by the prefrontal cortex (PFC). Overall, these studies have demonstrated that standard prefrontal neuroactivation tasks recruit a widely distributed network within the brain of which the PFC consistently forms a part. As such, these results are in keeping with the notion that executive functions within the PFC rely not only on anterior (mainly prefrontal) brain areas, but also on posterior (mainly parietal) brain regions. Moreover, intervention of similar brain regions in a large number of different executive tasks suggests that higher-level cognitive functions may best be understood in terms of an interactive network of specialised anterior as well as posterior brain regions.

Age-related differences in metabolites in the posterior cingulate cortex and hippocampus of normal ageing brain: A 1H-MRS study

OBJECTIVE To study age-related metabolic changes in N-acetylaspartate (NAA), total creatine (tCr), choline (Cho) and myo-inositol (Ins). MATERIALS AND METHODS Proton magnetic resonance spectroscopy (1H-MRS) was performed in the posterior cingulate cortex (PCC) and the left hippocampus (HC) of 90 healthy subjects (42 women and 48 men aged 18-76 years, mean±SD, 48.4±16.8 years). Both metabolite ratios and absolute metabolite concentrations were evaluated. Analysis of covariance (ANCOVA) and linear regression were used for statistical analysis. RESULTS Metabolite ratios Ins/tCr and Ins/H2O were found significantly increased with age in the PCC (P<0.05 and P≤0.001, respectively), and in the HC (P<0.01 for both). An increased tCr/H2O was only observed in the PCC (P<0.01). Following absolute quantification based on the internal water signal, significantly increased concentrations of Ins and tCr in the PCC confirmed the relative findings (P<0.01 for both). CONCLUSION Age-related increases of tCr and Ins are found in the PCC, whereas this holds only true for Ins in the HC, indicating possible gliosis in the ageing brain. No age-dependent NAA decreases were observed in the PCC nor the HC. The 1H-MRS results in these specific brain regions can be important to differentiate normal ageing from age-related pathologies such as mild cognitive impairment (MCI) and Alzheimers disease.