Detection of thirty-second cognitive activations in single subjects with positron emission tomography: a new low-dose H2(15)O regional cerebral blood flow three-dimensional imaging technique.

Positron emission tomography regional CBF (rCBF) studies of cognitive processes have traditionally required 30-60 mCi of H2(15)O per scan and intersubject averaging to achieve statistical significance. However, intersubject anatomical, functional, and disease variability can make such an approach problematic. A new method that produces significant results in single subjects is presented. It is based upon high-sensitivity three-dimensional imaging and a "slow" bolus administration of < 15 mCi of H2(15)O per scan. The method is validated in four normal volunteers using control and auditory-language activation tasks with four scans per condition and statistical parametric mapping analysis. It is demonstrated that the rCBF distribution associated with the cognitive state is detected during the arrival of radiotracer in the brain. This occurs over 30 s and constitutes a critical temporal window during which stimulation should be performed. A 90-s acquisition time is found to produce results of greater significance than a 60-s acquisition time. The implications of the results and the functional neuroanatomical findings are discussed. This method is suitable for the study of individual functional neuroanatomy in many neuropsychological, pharmacologic, and symptom states in normal subjects and in patients with psychiatric and neurologic disorders.

A rotating PET scanner using BGO block detectors: design, performance and applications.

Recent advances in fully three-dimensional reconstruction for multi-ring PET scanners have led us to explore the potential of a prototype scanner based on the rotation of two opposing arrays of BGO block detectors. The prototype contains only one-third of the number of detectors in the equivalent full ring scanner, resulting in reduced cost. With a lower energy threshold at 250 keV, the absolute efficiency of the scanner is 0.5% and the scatter fraction is 35% for a 20-cm cylinder. Transaxial and axial spatial resolution is about 6 mm. The maximum noise equivalent count rate estimated for a 15-cm diameter cylinder is 36,000 cps at a concentration of 26 kBq/ml. The minimum scan time for a 18F-fluoro-2-deoxyglucose (FDG) brain study is 55 sec. The camera has been validated for clinical applications using both FDG and 82Rb.

Assessment of response function in two PET scanners with and without interplane septa.

The authors have assessed the response function both experimentally and theoretically for two commercial tomographs: CTI 931/08-12 and CTI 953B with and without interplane septa. Monte Carlo simulations were undertaken using the GEANT package from CERN. Spatial resolution (tomographic and axial) was calculated for line sources at various positions in the field of view. Sensitivity and scatter fraction (SF) were calculated for various source geometries as a function of energy discrimination. A very realistic response function in positron emission tomography (PET) is obtained by Monte Carlo methods, using global parameters to account for unsimulated phenomena such as scintillation light transport inside a detector block and its sharing among the various phototubes. Minor discrepancies remain for sensitivity and SF at high energy thresholds and may probably be explained by introducing the observed dispersion in the energy response for the various crystals within a detector block.

Correction for scatter in 3D brain PET using a dual energy window method.

A method for scatter correction using dual energy window acquisition has been developed and implemented on data collected with a brain-PET tomograph operated in the septa retracted, 3D mode. Coincidence events are assigned to (i) an upper energy window where both photons deposit energy between 380 keV and 850 keV or (ii) a lower energy window where one or both photons deposit within 200 keV and 380 keV. Scaling parameters are derived from measurements of the ratios of counts from line sources due to scattered and unscattered events in the two energy windows in head-sized phantoms. A scaled subtraction of the two energy windows produces a distribution of scatter which is smoothed prior to subtraction from the upper energy window. In phantoms, the correction was found to restore the uniformity, contrast and linearity of activity concentration. Relative activity concentrations were restored to within 7% of their true values in a multicompartment phantom. The method was found to provide accurate correction for scattered events arising from activity outside the direct detector field of view. In a three-compartment phantom containing water, 18F and 11C scanned in dynamic, multiframe mode, the half-lives of the two isotopes were restored to within 2% of their true value.

Physical performance of a positron tomograph for brain imaging with retractable septa.

Performance characteristics of a new design of positron tomograph with automatically retractable septa for brain imaging have been studied. The device, consisting of block BGO detectors (8 x 8 elements per block), has a ring diameter of 76 cm and an axial FOV of 106.5 mm. The in-plane resolution is on average 5.8 mm and 5.0 mm (FWHM) for stationary and wobble sampling, respectively, over the central 18 cm of the transaxial FOV. Its unique feature is the capability of data acquisition both in the 'conventional' 2D mode (with septa) or 3D mode (septa retracted) where coincidences between any of the 16 detector rings are acquired. When scattered events are subtracted, the efficiency for a 20 cm diameter uniform cylinder increases overall by a factor of 4.8 between 2D (septa extended) and 3D modes. For a 20 cm phantom the trues/singles ratio is higher for 3D than for 2D but for a given unscattered trues rate, the randoms rate in 3D is higher. At 380 keV the scatter fraction within a 20 cm cylinder is 10% (septa extended) and 36% (retracted). In spite of the increase in scatter when septa are retracted, the increased efficiency in the 3D mode of acquisition yields distinct advantages, particularly in the many studies where tracer concentration is low and consequently where dead time and random rates are less important.

Performance evaluation of the positron scanner ECAT EXACT.

The Cologne Special is a prototype of the ECAT EXACT (model 921), a new generation of Siemens-CTI PET scanners. It consists of three rings of 48 BGO block detectors each, covering an axial field of view of 16.2 cm with a patient port of 56.2 cm diameter. This results in a total of 24 rings with 384 crystals each, giving 47 contiguous image planes in two-dimensional (2D) mode. Total system sensitivity is 216 kcps/microCi/ml for a 20 cm cylinder phantom in 2D. This increases to 1.5 Mcps/microCi/ml in 3D. Data are acquired in the stationary mode only (no wobble motion), resulting in a transaxial spatial resolution of better than 6 mm full width at half-maximum (FWHM) at the center, which degrades to 7.5 mm tangentially and 9.6 mm radially at a radius of 20 cm. Average axial resolution changes from 5.0 mm FWHM at the center to 8.1 mm at R = 20 cm. Count rate performance was investigated at different low energy discriminator settings and found to be linear up to 2.5 microCi/ml with a 20 cm phantom. The magnitude and distribution of scatter were evaluated for both septa-extended and septa-retracted conditions for a range of energy thresholds. Brain, heart, and whole-body studies with the new tomograph demonstrate the versatility of its applications without compromising on physical performance.

Characterization and correction of interpolation effects in the realignment of fMRI time series.

Subject motion in functional magnetic resonance imaging (fMRI) studies can be accurately estimated using realignment algorithms. However, residual changes in signal intensity arising from motion have been identified in the data even after realignment of the image time series. The nature of these artifacts is characterized using simulated displacements of an fMRI image and is attributed to interpolation errors introduced by the resampling inherent within realignment. A correction scheme that uses a periodic function of the estimated displacements to remove interpolation errors from the image time series on a voxel-by-voxel basis is proposed. The artifacts are investigated using a brain phantom to avoid physiological confounds. Small- and large-scale systematic displacements show that the artifacts have the same form as revealed by the simulated displacements. A randomly displaced phantom and a human subject are used to demonstrate that interpolation errors are minimized using the correction.

The effect of slice order and thickness on fMRI activation data using multislice echo-planar imaging.

Multislice echo-planar imaging (EPI) is a commonly used technique for fMRI studies. Brain activation images acquired using fMRI are sensitive to T2* changes, reflecting the level of blood oxygenation (BOLD contrast), and may also contain an element of T1 contrast which detects blood flow changes in large vessels. If slice inflow (T1) effects are significant in multislice EPI, then as the order in which the slices are acquired is changed, differences in the activation maps are predicted. However, in experiments presented here using visual stimulation, the data demonstrate that highly consistent results can be achieved for repetition times (TR) of 6.0, 3.0, and 1.5 s. This suggests that, for whole-brain multislice EPI, fMRI activation is dominated by T2*, BOLD contrast. The thickness of the imaging slice is also an important parameter in these studies, having implications for spatial resolution, sensitivity, and acquisition time. In separate visual cortex experiments the effect on the values of the fMRI Z scores and the number of activated voxels is investigated as a function of slice thickness (from 1 to 8 mm). The maximum Z scores in the data are similar for all slice thicknesses and, after resampling to allow a direct comparison to be made, the volume of visual cortex detected as significantly activated increases with slice thickness.

A functional neuroanatomy of hallucinations in schizophrenia.

Hallucinations, perceptions in the absence of external stimuli, are prominent among the core symptoms of schizophrenia. The neural correlates of these brief, involuntary experiences are not well understood, and have not been imaged selectively. We have used new positron emission tomography (PET) methods to study the brain state associated with the occurrence of hallucinations in six schizophrenic patients. Here we present a group study of five patients with classic auditory verbal hallucinations despite medication, demonstrating activations in subcortical nuclei (thalamic, striatal), limbic structures (especially hippocampus), and paralimbic regions (parahippocampal and cingulate gyri, as well as orbitofrontal cortex). We also present a case study of a unique, drug-naive patient with visual as well as auditory verbal hallucinations, demonstrating activations in visual and auditory/linguistic association cortices as part of a distributed cortical-subcortical network. Activity in deep brain structures, identified with group analysis, may generate or modulate hallucinations, and the particular neocortical regions entrained in individual patients may affect their specific perceptual content. The interaction of these distributed neural systems provides a biological basis for the bizarre reports of schizophrenic patients.

Regional cerebral blood flow during volitional expiration in man: a comparison with volitional inspiration.

1. Positron emission tomographic (PET) imaging of regional cerebral blood flow (rCBF), using a new 3-dimensional technique of data collection, was used to identify areas of neuronal activation associated with volitional inspiration and separately with volitional expiration in five normal male subjects. A comparison of the activated areas was also undertaken to isolate regions specific for one or other active task. 2. Scans were performed during intravenous infusion of H2(15)O under conditions of (a) volitional inspiration with passive expiration, (b) passive inspiration with volitional expiration and (c) passive inspiration with passive expiration. Four measurements in these three conditions were performed in each subject. Breathing pattern was well matched between conditions. 3. Regional increases in brain blood flow, due to increased neural activity associated with either active inspiration or active expiration, were derived using a pixel by pixel comparison of images obtained during the volitional and passive ventilation phases. Data were pooled from all runs in all subjects and were then processed to detect statistically significant (P < 0.05) increases in rCBF comparing active inspiration with passive inspiration and active expiration with passive expiration. 4. During active inspiration significant increases in rCBF were found bilaterally in the primary motor cortex dorsally just lateral to the vertex, in the supplementary motor area, in the right lateral pre-motor cortex and in the left ventrolateral thalamus. 5. In active expiration significant increases in rCBF were found in the right and left primary motor cortices dorsally just lateral to the vertex, the right and left primary motor cortices more ventrolaterally, the supplementary motor area, the right lateral pre-motor cortex, the ventrolateral thalamus bilaterally, and the cerebellum. 6. Using this modified and more sensitive PET technique, these findings essentially replicate those for volitional inspiration obtained in a previous study. For volitional expiration the areas activated are more extensive, but overlap with those involved in volitional inspiration. 7. The technique used has been successful in demonstrating the regions of the brain involved in the generation of volitional breathing, and probably in the volitional modulation of automatic breathing patterns such as would be required for the production of speech.

The development of in vivo tracer methods to obtain new information about human disease: a study of the hallucinating brain.

An outline is provided of the development of methodological strategies to address the question of focal cerebral activation during hallucinations in schizophrenic patients. In so doing, the innovation and diligence required to tailor in vivo tracer procedures to specific clinical research issues are highlighted. Attention is drawn to the complexity of methodological advances and the way in which they are based upon close scientific and technical collaboration between clinical scientists, and non-clinical scientists and research support staff.