A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.

/pdf/a-default-mode-of-brain-function-zwenkbmjw7.pdf

A default mode of brain function.

We propose an in vivo method for use with positron emission tomography (PET) that results in a quantitative characterization of neuroleptic binding sites using radiolabeled spiperone. The data are analyzed using a mathematical model that describes transport, nonspecific binding, and specific binding in the brain. The model demonstrates that the receptor quantities Bmax (i.e., the number of binding sites) and KD-1 (i.e., the binding affinity) are not separably ascertainable with tracer methodology in human subjects. We have, therefore, introduced a new term, the binding potential, equivalent to the product BmaxKD-1, which reflects the capacity of a given tissue, or region of a tissue, for ligand-binding site interaction. The procedure for obtaining these measurements is illustrated with data from sequential PET scans of baboons after intravenous injection of carrier-added (18F)spiperone. From these data we estimate the brain tissue nonspecific binding of spiperone to be in the range of 94.2 to 95.3%, and the regional brain spiperone permeability (measured as the permeability-surface area product) to be in the range of 0.025 to 0.036 cm3/(s X ml). The binding potential of the striatum ranged from 17.4 to 21.6; these in vivo estimates compare favorably to in vitro values in the literature. To ourmore » knowledge this represents the first direct evidence that PET can be used to characterize quantitatively, locally and in vivo, drug binding sites in brain. The ability to make such measurements with PET should permit the detailed investigation of diseases thought to result from disorders of receptor function.« less

A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography.

Across three experiments, PET scans were obtained while subjects performed different word-stem completion and FIXATION control tasks designed to study the functional anatomy of memory retrieval. During each of three different word-stem completion scans, word-stem cues were visually presented in uppercase letters. The RECALL task required explicit retrieval of study words presented prior to the PET scan. The PRIMING task addressed the implicit effects of the prior study words without requiring intentional recall. The BASELINE task encouraged retrieval of information from a general knowledge store. Across experiments, the similarity between study words and word stems was manipulated by presenting prescan study words in either uppercase letters identical to the stems, in lowercase letters, or auditorily. The PRIMING task was not studied with auditory presentation. Many activations were consistent across experiments. The BASELINE task activated several regions in response to the reading and verbal- response demands of the task (visual, motor, and premotor cortices, cerebellum), as well as a left prefrontal region. The RECALL task additionally activated regions in anterior right prefrontal cortex. Bilateral occipitotemporal regions showed blood flow reductions during the PRIMING task as compared to the BASELINE task. Activation in the right hippocampal/parahippocampal region was observed only in one experiment, and no experiment showed activation in the left medial temporal lobe. These experiments suggest that areas of frontal cortex play a role in explicit recall and that an effect of priming may be to require less activation of perceptual regions for the processing of recently presented information.

/pdf/functional-anatomical-studies-of-explicit-and-implicit-55s43q0c3u.pdf

Functional anatomical studies of explicit and implicit memory retrieval tasks

Significant improvements have made it possible to add the technology of time-of-flight (TOF) to improve PET, particularly for oncology applications. The goals of this work were to investigate the benefits of TOF in experimental phantoms and to determine how these benefits translate into improved performance for patient imaging. Methods: In this study we used a fully 3-dimensional scanner with the scintillator lutetium-yttrium oxyorthosilicate and a system timing resolution of ;600 ps. The data are acquired in list-mode and reconstructed with a maximum-likelihood expectation maximization algorithm; the system model includes the TOF kernel and corrections for attenuation, detector normalization, randoms, and scatter. The scatter correction is an extension of the model-based singlescatter simulation to include the time domain. Phantom measurements to study the benefit of TOF include 27-cm- and 35-cm-diameter distributions with spheres ranging in size from 10to37mm.ToassessthebenefitofTOFPETforclinicalimaging, patient studies are quantitatively analyzed. Results: The lesion phantom studies demonstrate the improved contrast of the smallest spheres with TOF compared with non-TOF and also confirm the faster convergence of contrast with TOF. These gains are evident from visual inspection of the images as well as a quantitative evaluation of contrast recovery of the spheres and noise in the background. The gains with TOF are higher for larger objects. These results correlate with patient studies in which lesions are seen more clearly and with higher uptake at comparable noise for TOF than with non-TOF. Conclusion: TOF leads to a better contrast-versus-noise trade-off than non-TOF but one that is difficult to quantify in terms of a simple sensitivity gain improvement: A single gain factor for TOF improvement does not include the increased rate of convergence with TOF nor does it consider that TOF may converge to a different contrast than non-TOF. The experimental phantom results agree with those of prior simulations and help explain the improved image quality with TOF for patient oncology studies.

https://jnm.snmjournals.org/content/jnumed/49/3/462.full.pdf

Benefit of Time-of-Flight in PET: Experimental and Clinical Results

Mathematical techniques are presented for the transformation of digital anatomical textbooks from the ideal to the individual, allowing for the representation of the variabilities manifest in normal human anatomies. The ideal textbook is constructed on a fixed coordinate system to contain all of the information currently available about the physical properties of neuroanatomies. This information is obtained via sensor probes such as magnetic resonance, as well as computed axial and emission tomography, along with symbolic information such as white- and gray-matter tracts, nuclei, etc. Human variability associated with individuals is accommodated by defining probabilistic transformations on the textbook coordinate system, the transformations forming mathematical translation groups of high dimension. The ideal is applied to the individual patient by finding the transformation which is consistent with physical properties of deformable elastic solids and which brings the coordinate system of the textbook to that of the patient. Registration, segmentation, and fusion all result automatically because the textbook carries symbolic values as well as multisensor features.

/pdf/mathematical-textbook-of-deformable-neuroanatomies-32m6kbknsi.pdf

Mathematical textbook of deformable neuroanatomies

We designed and built a positron emission transverse tomograph (PETT VI), designed specifically for fast dynamic studies in the human brain, and for cardiac studies in experimental animals. The scintillation detectors incorporated into this device are fitted with cesium fluoride crystals. Cesium fluoride was selected for this purpose because its short fluorescence decay allows the use of a short coincidence resolving time with a concomitant reduction of unwanted random coincidences. PETT VI utilizes four rings of 72 detectors simultaneously yielding seven tomographic sections. The system can be operated in either a low or high resolution mode with intrinsic geometrical resolutions in the plane of section of 7.1 to 11.7 mm full width at half maximum (FWHM), for a slice thickness with a resolution at the center of 13.9 mm FWHM. The maximum sensitivity of the system for seven slices in the low resolution mode is 322,000 cps/microCi/cc in a 20 cm diameter phantom. The contribution of random coincidences before subtraction in PETT VI was found to be approximately 14% of the counts in the phantom image with a source of approximately 3.5 mCi of a positron emitting radionuclide dispersed in a 20 cm diameter tissue equivalent phantom with a concentration of 1 microCi/cc. The short coincidence resolving time of the system permits rapid data acquisition for attenuation corrections and clinical dynamic studies with data acquisition times of less than a minute.

PETT VI: a positron emission tomograph utilizing cesium fluoride scintillation detectors.

The physical characteristics and some imaging capabilities of Super PETT I, a positron emission tomograph utilizing time-of-flight (TOF) in its image reconstruction process were assessed experimentally by means of measurements carried out in phantoms and clinical imaging studies. The performance characteristics assessed included sensitivity, spatial resolution, image improvements resulting from time-of-flight information utilization, system dead time, and linearity. The clinical examples included imaging of the brain, the heart, the liver, and a demonstration of Super PETT I's capability of achieving cardiac gating.

Super PETT I: A Positron Emission Tomograph Utilizing Photon Time-of-Flight Information

A simple 18O water target for 18F production.

Imaging of the brain by positron emission tomography can be optimized for sensitivity by dedicating the design of the tomograph to this application. We have designed a multislice positron emission tomograph (PETT V) for imaging the human brain and the whole body of small experimental animals. The detector system of PETT V consists of a circular array of 48 NaI(Tl) scintillation detectors, each fitted with two photomultiplier tubes, with one dimensional positioning capability. Suitable sampling is achieved by rotation of the circular array of detectors and by a wobbling motion of the detector circle. The proposed system is capable of providing seven slices simultaneously, with a spatial resolution in the plane of the slice from 7 to 15 mm and with slice thicknesses of 7 and 14 mm. The minimum scanning time is 1 sec. The estimated overall sensitivity of PETT V is 350,000 counts/sec/mCi in a 20 cm diameter phantom for a resolution of approximately 1.5 x 1.5 cm. The system is under construction.

Design considerations for a positron emission transverse tomograph (PETT V) for imaging of the brain

We designed, built, and tested a positron emission tomograph (PETT IV) capable of providing seven slices of the human body simultaneously. PETT IV utilizes a moving hexagonal array of 48 scintillation detectors placed around the subject. Each detector consists of a cylindrical activated sodium iodide crystal optically coupled to two photomultiplier tubes. The multislice capability is achieved by comparing the light outputs of the two photomultiplier tubes in each detector. The images are displayed either as transverse or as longitudinal tomographic sections. This system provides high sensitivity and resolution, and permits rapid and accurate three-dimensional imaging of the head and body.

John T. Hood

Papers

PETT VI: a positron emission tomograph utilizing cesium fluoride scintillation detectors.

Super PETT I: A Positron Emission Tomograph Utilizing Photon Time-of-Flight Information

A simple 18O water target for 18F production.

Design considerations for a positron emission transverse tomograph (PETT V) for imaging of the brain

A Multislice Positron Emission Computed Tomograph (PETT IV) Yielding Transverse and Longitudinal Images