Classification of schizophrenic patients and healthy controls using [18F] fluorodopa PET imaging.

Striatal dopaminergic overactivity has been implicated in the pathophysiology of schizophrenia on the basis of in vivo neuroimaging studies. In particular, elevated striatal dopamine synthesis and storage has been repeatedly demonstrated in schizophrenia using the radiotracer 6-[18F] fluoro-l-DOPA ([18F] DOPA) and positron emission tomography (PET). Conventionally analysed [18F] DOPA PET imaging lacks the sensitivity or specificity to be used diagnostically.

A survey of approaches for direct parametric image reconstruction in emission tomography.

The quantitative data obtained by emission tomography are decoded using a number of techniques and methods in sequence to provide physiological information. Conventionally, the data are reconstructed to produce a series of static images. Then, pharmacokinetic modeling techniques are applied, and kinetic parameters that have physiological or functional significance are derived.

Microglia, amyloid, and cognition in Alzheimer's disease: An [11C](R)PK11195-PET and [11C]PIB-PET study.

[11C](R)PK11195-PET is a marker of activated microglia while [11C]PIB-PET detects raised amyloid load. Here we studied in vivo the distributions of amyloid load and microglial activation in Alzheimer's disease (AD) and their relationship with cognitive status. Thirteen AD subjects had [11C](R)PK11195-PET and [11C]PIB-PET scans.

Novel reference region model reveals increased microglial and reduced vascular binding of 11C-(R)-PK11195 in patients with Alzheimer's disease.

Unlabelled: 11C-(R)-PK11195 is a PET radiotracer for the quantification of peripheral benzodiazepine binding sites (PBBSs). The PBBS is a consistent marker of activated microglia, and 11C-(R)-PK11195 has been used to image microglial activity in the diseased brain and in neoplasia. However, the PBBS is also expressed in the brain vasculature (endothelium and smooth muscles), and no evidence, to our knowledge, exists of a change in the vascular PBBS in pathologic brains or of such a change having an effect on the quantification of 11C-(R)-PK11195 binding.

Study of direct and indirect parametric estimation methods of linear models in dynamic positron emission tomography.

In dynamic positron emission tomography (PET) studies, the time changing activity of the radiotracer is measured through multiple consecutive frames. Subsequent pixel-by-pixel application of the appropriate kinetic model provides quantitative information in terms of images of the distribution of the physiological parameter of interest. In this context, iterative reconstruction methods may be used to reconstruct for each time frame a static image of appreciable higher quality than the analytical algorithms, especially in low-count cases.

PET image denoising using a synergistic multiresolution analysis of structural (MRI/CT) and functional datasets.

Unlabelled: PET allows the imaging of functional properties of the living tissue, whereas other modalities (CT, MRI) provide structural information at significantly higher resolution and better image quality. Constraints for injected radioactivity, technologic limitations of current instrumentation, and inherent spatial uncertainties on the decaying process affect the quality of PET images. In this article we illustrate how structural information of matched anatomic images can be used in a multiresolution model to enhance the signal-to-noise ratio of PET images.

Chromosomal profiles of gene expression in Huntington's disease.

Recent studies suggested that Huntington's disease is due to aberrant interactions between mutant huntingtin protein, transcription factors and transcriptional co-activators resulting in widespread transcriptional dysregulation. Mutant huntingtin also interacts with histone acetyltransferases, consequently interfering with the acetylation and deacetylation states of histones. Because histone modifications and chromatin structure coordinate the expression of gene clusters, we have applied a novel mathematical approach, Chromowave, to analyse microarray datasets of brain tissue and whole blood to understand how genomic regions are altered by the effects of mutated huntingtin on chromatin structure.

A common system for the comprehension and production of narrative speech.

Humans devote much time to the exchange of memories within the context of shared general and personal semantic knowledge. Our hypothesis was that functional imaging in normal subjects would demonstrate the convergence of speech comprehension and production on high-order heteromodal and amodal cortical areas implicated in declarative memory functions. Activity independent of speech phase (that is, comprehension and production) was most evident in the left and right lateral anterior temporal cortex.

Volumes, spatial extents and a probabilistic atlas of the human basal ganglia and thalamus.

The basal ganglia and thalamus are involved in processing all physiological behaviors and affected by many diseases. Accurate localization is a crucial issue in neuroimaging, particularly when working with groups of normalized images in a standard stereotaxic space. Here, manual delineation of the central structures (thalamus; nucleus caudatus and accumbens; putamen, pallidum, substantia nigra) was performed on 30 high resolution MRIs of healthy young adults (15 female, median age 31 years) in native space.

Balancing bias, reliability, noise properties and the need for parametric maps in quantitative ligand PET: [(11)C]diprenorphine test-retest data.

[(11)C]diprenorphine (DPN) is a non-subtype selective opioid receptor PET ligand with slow kinetics and no region devoid of specific binding. Parametric maps are desirable but have to overcome high noise at the voxel level. We obtained parameter values, parametric map image quality, test-retest reproducibility and reliability (using intraclass correlation coefficients (ICCs)) for conventional spectral analysis and a derived method (rank shaping), compared them with values obtained through sampling of volumes of interest (VOIs) on the dynamic data sets and tested whether smaller amounts of radioactivity injected maintained reliability.

[11C]Flumazenil PET in temporal lobe epilepsy: do we need an arterial input function or kinetic modeling?

Reduced signal on [(11)C]]flumazenil (FMZ) positron emission tomography (PET) is associated with epileptogenic foci. Linear correlations within individuals between parametric and nonparametric images of FMZ binding have been shown, and various methods have been used, without comparison of diagnostic usefulness. Using hippocampal sclerosis (HS) as a test case, we formally compare the diagnostic yield of parametric images obtained either with a parent tracer arterial plasma input function and spectral analysis (yielding volume-of-distribution (VD) images), or with an image-based input function and the simplified reference tissue model (binding potential images, BP-SRTM) with the diagnostic yield of semiquantitative-integrated (ADD) images from 10 to 20 or 20 to 40 mins (ADD1020 and ADD2040).

The lack of expression of the peripheral benzodiazepine receptor characterises microglial response in anaplastic astrocytomas.

The peripheral benzodiazepine receptor (PBR) is a 18 kDa molecule mainly involved in cholesterol transport through the mitochondrial membrane. In microglia, PBR is expressed from the earliest stages of activation and appears to exert a pro-inflammatory function. This molecule is commonly up-regulated in inflammatory, degenerative, infective and ischaemic lesions of the central nervous system but it has never been reported in glioma-infiltrating microglia.

A systematic comparison of kinetic modelling methods generating parametric maps for [(11)C]-(R)-PK11195.

[(11)C]-(R)-PK11195 is presently the most widely used radiotracer for the monitoring of microglia activity in the central nervous system (CNS). Microglia, the resident immune cells of the brain, play a critical role in acute and chronic diseases of the central nervous system and in host defence against neoplasia. The purpose of this investigation was to evaluate the reliability and sensitivity of five kinetic modelling methods for the formation of parametric maps from dynamic [(11)C]-(R)-PK11195 studies.

A review of the functional role and of the expression profile of retinoid signaling and of nuclear receptors in human spinal cord.

Spinal cord degenerative pathologies in humans cause extensive disability and require a broad range of specialist and palliative medical interventions. In amyotrophic lateral sclerosis (ALS), motor cell loss leads to extensive paralysis and to death from respiratory failure in 3-5 years form disease onset. A wide range of molecular changes forms the basis of spinal cord involvement in ALS, including the reactivation of molecular pathways with potentially neurorestorative properties.

Reference and target region modeling of [11C]-(R)-PK11195 brain studies.

Unlabelled: PET with [(11)C]-(R)-PK11195 is currently the modality of choice for the in vivo imaging of microglial activation in the human brain. In this work we devised a supervised clustering procedure and a new quantification methodology capable of producing binding potential (BP) estimates quantitatively comparable with those derived from plasma input with robust quantitative implementation at the pixel level.

Methods: The new methodology uses predefined kinetic classes to extract a gray matter reference tissue without specific tracer binding and devoid of spurious signals (in particular, blood pool and muscle).

Chromosomal patterns of gene expression from microarray data: methodology, validation and clinical relevance in gliomas.

Background: Expression microarrays represent a powerful technique for the simultaneous investigation of thousands of genes. The evidence that genes are not randomly distributed in the genome and that their coordinated expression depends on their position on chromosomes has highlighted the need for mathematical approaches to exploit this dependency for the analysis of expression data-sets.

Results: We have devised a novel mathematical technique (CHROMOWAVE) based on the Haar wavelet transform and applied it to a dataset obtained with the Affymetrix HG-U133_Plus_2 array in 27 gliomas.

Correction of head movement on PET studies: comparison of methods.

Unlabelled: Head movement presents a continuing problem in PET studies. Head restraint minimizes movement but is unreliable, resulting in the need to develop alternative strategies. These include frame-by-frame (FBF) realignment or use of motion tracking (MT) during the scan to realign PET acquisition data.

Converging language streams in the human temporal lobe.

There is general agreement that, after initial processing in unimodal sensory cortex, the processing pathways for spoken and written language converge to access verbal meaning. However, the existing literature provides conflicting accounts of the cortical location of this convergence. Most aphasic stroke studies localize verbal comprehension to posterior temporal and inferior parietal cortex (Wernicke's area), whereas evidence from focal cortical neurodegenerative syndromes instead implicates anterior temporal cortex.

Microglial activation correlates with severity in Huntington disease: a clinical and PET study.

Background: Huntington disease (HD) is characterized by the progressive death of medium spiny dopamine receptor bearing striatal GABAergic neurons. In addition, microglial activation in the areas of neuronal loss has recently been described in postmortem studies. Activated microglia are known to release neurotoxic cytokines, and these may contribute to the pathologic process.

Multi-resolution Bayesian regression in PET dynamic studies using wavelets.

In the kinetic analysis of dynamic PET data, one usually posits that the variation of the data through one dimension, time, can be described by a mathematical model encapsulating the relevant physiological features of the radioactive tracer. In this work, we posit that the remaining dimension, space, can also be modeled as a physiological feature, and we introduce this concept into a new computational procedure for the production of parametric maps. An organ and, in the instance considered here, the brain presents similarities in the physiological properties of its elements across scales: computationally, this similarity can be implemented in two stages.

HBM functional imaging analysis contest data analysis in wavelet space.

An analysis of the Functional Imaging Analysis Contest (FIAC) data is presented using spatial wavelet processing. This technique allows the image to be filtered adaptively according to the data itself, rather than relying on a predetermined filter. This adaptive filtering leads to better estimation of the parameters and contrasts in terms of mean squared error.

Quantification of subendocardial and subepicardial blood flow using 15O-labeled water and PET: experimental validation.

Unlabelled: The purpose of this study was to assess the feasibility and accuracy of quantifying subendocardial and subepicardial myocardial blood flow (MBF) and the relative coronary flow reserves (CFR) using (15)O-labeled water (H(2)(15)O) and 3-dimensional-only PET.

Methods: Eight pigs were scanned with H(2)(15)O and (15)O-labeled carbon monoxide (C(15)O) after partially occluding the circumflex (n = 3) or the left anterior descending (n = 5) coronary artery, both at rest and during hyperemia induced by intravenous dipyridamole. Radioactive microspheres were injected during each of the H(2)(15)O scans.

In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease.

Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder associated with akinesia, tremor and rigidity. While the characteristic Lewy body pathology targets pigmented and other brainstem nuclei at post-mortem, activated microglia are found in both subcortical and cortical areas. [11C](R)-PK11195 is a positron emission tomography (PET) marker of peripheral benzodiazepine sites (PBBS), which are selectively expressed by activated microglia.

In vivo imaging of microglial activation with [11C](R)-PK11195 PET in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative disease presenting with voluntary gaze difficulties, early falls, and Parkinsonism. Neuronal loss, associated with intracellular neurofibrillary tangles and activated microglia, is found targeting the basal ganglia, brainstem nuclei, and frontal cortex. [11C](R)-PK11195 PET is a marker of peripheral benzodiazepine binding sites (PBBS) expressed by activated microglia.